ClinVar Miner

Submissions for variant NM_000090.4(COL3A1):c.3806A>G (p.His1269Arg)

dbSNP: rs751092650
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002310843 SCV000318327 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2016-10-10 criteria provided, single submitter clinical testing The p.H1269R variant (also known as c.3806A>G), located in coding exon 48 of the COL3A1 gene, results from an A to G substitution at nucleotide position 3806. The histidine at codon 1269 is replaced by arginine, an amino acid with highly similar properties. Based on data from ExAC, the G allele has an overall frequency of less than 0.01% (1/105450). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV002518682 SCV003454651 uncertain significance Ehlers-Danlos syndrome, type 4 2023-08-08 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 1269 of the COL3A1 protein (p.His1269Arg). This variant is present in population databases (rs751092650, gnomAD 0.0009%). 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: 263525). 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.

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