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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
ClinVar Genomic variation as it relates to human health
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- Interpretation:
-
Uncertain significance
- Review status:
- criteria provided, multiple submitters, no conflicts
- Submissions:
- 3
- First in ClinVar:
- Dec 27, 2015
- Most recent Submission:
- Feb 7, 2023
- Last evaluated:
- Sep 22, 2022
- Accession:
- VCV000218759.8
- Variation ID:
- 218759
- Description:
- single nucleotide variant
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NM_018714.3(COG1):c.1117G>A (p.Val373Met)
- Allele ID
- 215543
- Variant type
- single nucleotide variant
- Variant length
- 1 bp
- Cytogenetic location
- 17q25.1
- Genomic location
- 17: 73200612 (GRCh38) GRCh38 UCSC
- 17: 71196751 (GRCh37) GRCh37 UCSC
- HGVS
-
Nucleotide Protein Molecular
consequenceNM_018714.3:c.1117G>A MANE Select NP_061184.1:p.Val373Met missense NC_000017.11:g.73200612G>A NC_000017.10:g.71196751G>A NG_008971.1:g.12579G>A - Protein change
- V373M
- Other names
- -
- Canonical SPDI
- NC_000017.11:73200611:G:A
- Functional consequence
- -
- Global minor allele frequency (GMAF)
- 0.00020 (A)
- Allele frequency
- The Genome Aggregation Database (gnomAD) 0.00022
- Trans-Omics for Precision Medicine (TOPMed) 0.00021
- The Genome Aggregation Database (gnomAD) 0.00013
- 1000 Genomes Project 0.00020
- NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00015
- Trans-Omics for Precision Medicine (TOPMed) 0.00024
- Links
- ClinGen: CA248961
- dbSNP: rs201886877
- VarSome
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Aggregate interpretations per condition
| Interpreted condition | Interpretation | Number of submissions | Review status | Last evaluated | Variation/condition record |
|---|---|---|---|---|---|
| Uncertain significance | 2 | criteria provided, multiple submitters, no conflicts | Sep 22, 2022 | RCV000391472.8 | |
| Uncertain significance | 1 | criteria provided, single submitter | Jun 17, 2015 | RCV000202771.1 |
Submitted interpretations and evidence
Help| Interpretation (Last evaluated) |
Review status (Assertion criteria) |
Condition (Inheritance) |
Submitter | More information | |
|---|---|---|---|---|---|
|
Uncertain significance
(Jun 17, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Affected status: unknown
Allele origin:
unknown
|
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia
Accession: SCV000258138.2
First in ClinVar: Dec 27, 2015 Last updated: Dec 27, 2015 |
|
|
|
Uncertain significance
(Jan 12, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000406283.3
First in ClinVar: Dec 06, 2016 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
|
|
|
Uncertain significance
(Sep 22, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001375392.3
First in ClinVar: Jul 16, 2020 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 373 of the COG1 protein (p.Val373Met). … (more)
This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 373 of the COG1 protein (p.Val373Met). This variant is present in population databases (rs201886877, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with COG1-related conditions. ClinVar contains an entry for this variant (Variation ID: 218759). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt COG1 protein function. 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)
|
Functional evidence
Help| 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 this variant
Help| There are no citations in ClinVar for this variation. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs201886877...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Apr 09, 2023