ClinVar Miner

Submissions for variant NM_000090.4(COL3A1):c.884C>T (p.Ala295Val)

gnomAD frequency: 0.00001  dbSNP: rs1016767830
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001186412 SCV001352814 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2019-10-02 criteria provided, single submitter clinical testing This missense variant replaces alanine with valine at codon 295 of the COL3A1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, 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 been identified in 1/250992 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.
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV001197892 SCV001368675 uncertain significance Polymicrogyria with or without vascular-type Ehlers-Danlos syndrome 2019-01-29 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PP2.
MGZ Medical Genetics Center RCV002290622 SCV002579177 uncertain significance Ehlers-Danlos syndrome, type 4 2022-05-18 criteria provided, single submitter clinical testing
Invitae RCV002290622 SCV004304250 uncertain significance Ehlers-Danlos syndrome, type 4 2023-07-10 criteria provided, single submitter clinical testing 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 not expected to disrupt 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. ClinVar contains an entry for this variant (Variation ID: 924824). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 295 of the COL3A1 protein (p.Ala295Val). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with COL3A1-related conditions.

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