ClinVar Miner

Submissions for variant NM_000090.4(COL3A1):c.497T>A (p.Val166Glu)

gnomAD frequency: 0.00001  dbSNP: rs1016172772
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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 RCV001191970 SCV001359913 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-03-15 criteria provided, single submitter clinical testing This missense variant replaces valine with glutamic acid at codon 166 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). 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 2/251066 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 RCV002560992 SCV003473531 uncertain significance Ehlers-Danlos syndrome, type 4 2023-07-21 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 928201). This variant has not been reported in the literature in individuals affected with COL3A1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces valine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 166 of the COL3A1 protein (p.Val166Glu).
All of Us Research Program, National Institutes of Health RCV002560992 SCV004832973 uncertain significance Ehlers-Danlos syndrome, type 4 2023-06-26 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This missense variant replaces valine with glutamic acid at codon 166 of the COL3A1 protein. Computational prediction tools and conservation analyses suggest that this variant may have deleterious impact on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 2/245844 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.

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