ClinVar Miner

Submissions for variant NM_000090.4(COL3A1):c.3466C>T (p.His1156Tyr)

gnomAD frequency: 0.00003  dbSNP: rs776814693
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000818384 SCV000958994 uncertain significance Ehlers-Danlos syndrome, type 4 2022-05-11 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 1156 of the COL3A1 protein (p.His1156Tyr). This variant is present in population databases (rs776814693, gnomAD 0.04%). 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: 661052). 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.
Ambry Genetics RCV002460111 SCV002618424 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2018-11-20 criteria provided, single submitter clinical testing The p.H1156Y variant (also known as c.3466C>T), located in coding exon 47 of the COL3A1 gene, results from a C to T substitution at nucleotide position 3466. The histidine at codon 1156 is replaced by tyrosine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and tyrosine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health RCV000818384 SCV004815729 uncertain significance Ehlers-Danlos syndrome, type 4 2023-12-01 criteria provided, single submitter clinical testing This missense variant replaces histidine with tyrosine at codon 1156 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 13/250868 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.

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