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:
- 2
- First in ClinVar:
- May 31, 2020
- Most recent Submission:
- Feb 7, 2023
- Last evaluated:
- Jul 19, 2022
- Accession:
- VCV000892412.5
- Variation ID:
- 892412
- Description:
- single nucleotide variant
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NM_018714.3(COG1):c.1784G>T (p.Gly595Val)
- Allele ID
- 878350
- Variant type
- single nucleotide variant
- Variant length
- 1 bp
- Cytogenetic location
- 17q25.1
- Genomic location
- 17: 73201611 (GRCh38) GRCh38 UCSC
- 17: 71197750 (GRCh37) GRCh37 UCSC
- HGVS
-
Nucleotide Protein Molecular
consequenceNM_018714.3:c.1784G>T MANE Select NP_061184.1:p.Gly595Val missense NC_000017.11:g.73201611G>T NC_000017.10:g.71197750G>T NG_008971.1:g.13578G>T - Protein change
- G595V
- Other names
- -
- Canonical SPDI
- NC_000017.11:73201610:G:T
- Functional consequence
- -
- Global minor allele frequency (GMAF)
- -
- Allele frequency
- The Genome Aggregation Database (gnomAD), exomes 0.00002
- Exome Aggregation Consortium (ExAC) 0.00002
- Links
- dbSNP: rs752197597
- 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 | Jul 19, 2022 | RCV001128424.5 |
Submitted interpretations and evidence
Help| Interpretation (Last evaluated) |
Review status (Assertion criteria) |
Condition (Inheritance) |
Submitter | More information | |
|---|---|---|---|---|---|
|
Uncertain significance
(Jan 13, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
COG1 congenital disorder of glycosylation
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services,Illumina
Accession: SCV001287866.1
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, 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
(Jul 19, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
COG1 congenital disorder of glycosylation
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV003475970.1
First in ClinVar: Feb 07, 2023 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 595 of the COG1 protein (p.Gly595Val). … (more)
This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 595 of the COG1 protein (p.Gly595Val). This variant is present in population databases (rs752197597, gnomAD 0.01%). 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: 892412). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 rs752197597...
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