ClinVar Miner

Submissions for variant NM_000090.4(COL3A1):c.2974C>A (p.Arg992Ser)

gnomAD frequency: 0.00001  dbSNP: rs1431359737
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001526156 SCV001736453 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-03-30 criteria provided, single submitter clinical testing This missense variant replaces arginine with serine at codon 992 of the COL3A1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with COL3A1-related disorders in the literature. This variant has been identified in 1/31404 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV002488346 SCV002792279 uncertain significance Ehlers-Danlos syndrome, type 4; Polymicrogyria with or without vascular-type Ehlers-Danlos syndrome 2021-10-29 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004008892 SCV004826083 uncertain significance Ehlers-Danlos syndrome, type 4 2023-12-01 criteria provided, single submitter clinical testing This missense variant replaces arginine with serine at codon 992 of the COL3A1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 1/31404 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV004008892 SCV005817332 uncertain significance Ehlers-Danlos syndrome, type 4 2024-07-02 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 992 of the COL3A1 protein (p.Arg992Ser). This variant is present in population databases (no rsID available, gnomAD 0.007%). This missense change has been observed in individual(s) with vascular Ehlers-Danlos syndrome (PMID: 37079061). ClinVar contains an entry for this variant (Variation ID: 1172341). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on COL3A1 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.
PreventionGenetics, part of Exact Sciences RCV004541978 SCV004799966 uncertain significance COL3A1-related disorder 2023-11-08 no assertion criteria provided clinical testing The COL3A1 c.2974C>A variant is predicted to result in the amino acid substitution p.Arg992Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0065% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-189870118-C-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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