ClinVar Miner

Submissions for variant NM_000090.4(COL3A1):c.3763C>T (p.Arg1255Cys)

dbSNP: rs1576473569
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001181091 SCV001346168 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-03-15 criteria provided, single submitter clinical testing This missense variant replaces arginine with cysteine at codon 1255 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 not been identified 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.
PreventionGenetics, part of Exact Sciences RCV004538410 SCV004118233 likely pathogenic COL3A1-related disorder 2023-09-14 criteria provided, single submitter clinical testing The COL3A1 c.3763C>T variant is predicted to result in the amino acid substitution p.Arg1255Cys. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. A different missense variant affecting the same amino acid (p.Arg1255His) was reported in an individual with sporadic thoracic aortic dissection; however, no additional evidence was provided to support causation (Chen. 2021. PubMed ID: 34047934). Taken together, the c.3763C>T (p.Arg1255Cys) variant is interpreted as likely pathogenic.
All of Us Research Program, National Institutes of Health RCV004006717 SCV004827536 uncertain significance Ehlers-Danlos syndrome, type 4 2023-04-03 criteria provided, single submitter clinical testing This missense variant replaces arginine with cysteine at codon 1255 of the COL3A1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified 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.

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