ClinVar Miner

Submissions for variant NM_000090.4(COL3A1):c.4066T>G (p.Phe1356Val)

dbSNP: rs945183835
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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 RCV001182131 SCV001347485 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-12-05 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This missense variant replaces phenylalanine with valine at codon 1356 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 is rare in the general population and has been identified in 0/277264 chromosomes by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively.
Labcorp Genetics (formerly Invitae), Labcorp RCV001338238 SCV001531890 uncertain significance Ehlers-Danlos syndrome, type 4 2024-02-26 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1356 of the COL3A1 protein (p.Phe1356Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with COL3A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 922200). 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.
Phosphorus, Inc. RCV001823762 SCV002073474 uncertain significance not specified 2022-01-18 criteria provided, single submitter clinical testing This missense variant results in a substitution of phenylalanine with valine at codon 1356 of the COL3A1 gene (transcript NM_000090.3). This variant has been reported in ClinVar (922200) NM_000090.4 (COL3A1):c.4066T>G (p.Phe1356Val). The variant has not occurred in population databases. This position is conserved. In silico functional algorithms agree, predicting it as possibly damaging (PolyPhen) and deleterious (SIFT), but no functional studies were performed to confirm these predictions. The variant has not occurred in the literature associated with the disease. In conclusion, the available evidence is insufficient to determine the pathogenicity of this variant. Therefore, it is classified as a Variant of Uncertain Significance.

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