ClinVar Genomic variation as it relates to human health
NM_003919.3(SGCE):c.391A>G (p.Ile131Val)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Uncertain significance(6); Benign(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_003919.3(SGCE):c.391A>G (p.Ile131Val)
Variation ID: 374642 Accession: VCV000374642.43
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7q21.3 7: 94623397 (GRCh38) [ NCBI UCSC ] 7: 94252709 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Oct 10, 2018 May 12, 2024 Jan 16, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_003919.3:c.391A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003910.1:p.Ile131Val missense NM_001099400.2:c.391A>G NP_001092870.1:p.Ile131Val missense NM_001099401.2:c.391A>G NP_001092871.1:p.Ile131Val missense NM_001301139.2:c.268A>G NP_001288068.1:p.Ile90Val missense NM_001346713.2:c.499A>G NP_001333642.1:p.Ile167Val missense NM_001346715.2:c.499A>G NP_001333644.1:p.Ile167Val missense NM_001346717.2:c.391A>G NP_001333646.1:p.Ile131Val missense NM_001346719.2:c.304A>G NP_001333648.1:p.Ile102Val missense NM_001346720.2:c.118A>G NP_001333649.1:p.Ile40Val missense NM_001362807.2:c.304A>G NP_001349736.1:p.Ile102Val missense NM_001362808.2:c.118A>G NP_001349737.1:p.Ile40Val missense NM_001362809.2:c.268A>G NP_001349738.1:p.Ile90Val missense NC_000007.14:g.94623397T>C NC_000007.13:g.94252709T>C NG_008893.2:g.37813A>G LRG_206t1:c.391A>G LRG_206p1:p.Ile131Val - Protein change
- I131V, I167V, I102V, I40V, I90V
- Other names
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- Canonical SPDI
- NC_000007.14:94623396:T:C
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00015
The Genome Aggregation Database (gnomAD) 0.00015
The Genome Aggregation Database (gnomAD), exomes 0.00018
Trans-Omics for Precision Medicine (TOPMed) 0.00019
Exome Aggregation Consortium (ExAC) 0.00027
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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SGCE | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
66 | 651 | |
CASD1 | - | - |
GRCh38 GRCh37 |
28 | 615 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Uncertain significance (4) |
criteria provided, multiple submitters, no conflicts
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Apr 1, 2017 | RCV000416039.24 | |
Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Jan 16, 2024 | RCV000689645.16 | |
Uncertain significance (1) |
criteria provided, single submitter
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Nov 10, 2022 | RCV002469145.2 | |
Uncertain significance (1) |
criteria provided, single submitter
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Aug 10, 2023 | RCV003362776.2 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
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The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Uncertain significance
(Apr 01, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV000493494.28
First in ClinVar: Jan 30, 2017 Last updated: May 12, 2024 |
Number of individuals with the variant: 1
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Uncertain significance
(Oct 10, 2016)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000701959.2
First in ClinVar: Apr 02, 2018 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Benign
(Jan 13, 2018)
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criteria provided, single submitter
Method: clinical testing
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Myoclonic dystonia 11
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001327355.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
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Uncertain significance
(Nov 10, 2022)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002766237.1
First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022 |
Comment:
Variant summary: SGCE c.391A>G (p.Ile131Val) results in a conservative amino acid change located in the dystroglycan-type cadherin-like domain (IPR006644) of the encoded protein sequence. Three … (more)
Variant summary: SGCE c.391A>G (p.Ile131Val) results in a conservative amino acid change located in the dystroglycan-type cadherin-like domain (IPR006644) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant is located near a canonical splice site and therefore may affect splicing. Several computational tools predict a significant impact on normal splicing: Three predict the variant creates a 5 prime donor site, whereas three predict the variant strengthens the canonical 3 prime acceptor site. These predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00018 in 247766 control chromosomes, predominantly at a frequency of 0.00037 within the Non-Finnish European subpopulation in the gnomAD database. This frequency is higher than would be expected for a rare autosomal dominant disorder, suggesting the variant may be benign. However it should be noted that in SGCE-related Myoclonic Dystonia, penetrance is determined by parental origin of the altered allele due to maternal imprinting, therefore a pathogenic variant on the maternally-derived SGCE allele typically does not result in the disease phenotype (Raymond_2003, Gene Reviews), making it difficult to interpret whether the frequency of the c.391A>G variant in the control population allows for any conclusion about variant significance. To our knowledge, no occurrence of c.391A>G in individuals affected with Myoclonic Dystonia and no experimental evidence demonstrating its impact on protein function have been reported. Four submitters have provided clinical-significance assessments for this variant to ClinVar after 2014. Three classified the variant as VUS and one classified it as benign. Based on the evidence outlined above, the variant was classified as uncertain significance. (less)
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Uncertain significance
(Dec 03, 2021)
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criteria provided, single submitter
Method: clinical testing
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Myoclonic dystonia 11
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV003819903.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Uncertain significance
(Jan 16, 2024)
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criteria provided, single submitter
Method: clinical testing
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Myoclonic dystonia 11
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000817308.7
First in ClinVar: Oct 10, 2018 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 131 of the SGCE protein (p.Ile131Val). … (more)
This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 131 of the SGCE protein (p.Ile131Val). This variant is present in population databases (rs370609227, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with SGCE-related conditions. ClinVar contains an entry for this variant (Variation ID: 374642). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
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Uncertain significance
(Aug 10, 2023)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV004053006.2
First in ClinVar: Oct 28, 2023 Last updated: May 01, 2024 |
Comment:
The c.391A>G (p.I131V) alteration is located in exon 4 (coding exon 4) of the SGCE gene. This alteration results from a A to G substitution … (more)
The c.391A>G (p.I131V) alteration is located in exon 4 (coding exon 4) of the SGCE gene. This alteration results from a A to G substitution at nucleotide position 391, causing the isoleucine (I) at amino acid position 131 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less)
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Uncertain significance
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001798903.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
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Uncertain significance
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001966902.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=SGCE | - | - | - | - |
Text-mined citations for rs370609227 ...
HelpRecord last updated May 12, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.