ClinVar Miner

Submissions for variant NM_000393.5(COL5A2):c.437G>A (p.Arg146Gln) (rs144430633)

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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 RCV000618775 SCV000738745 uncertain significance Cardiovascular phenotype 2017-09-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
GeneDx RCV000200613 SCV000250024 uncertain significance not provided 2018-12-06 criteria provided, single submitter clinical testing TAAD is a genetically heterogeneous disorder characterized by aortic dilatation, aneurysms, dissections and/or aneurysms of other major arteries. Approximately 4% of patients with autosomal dominant Ehlers-Danlos syndrome, classic type, have been reported to have a mutation in the COL5A2 gene (Malfait F et al., 2011). p.Arg146Gln (CGA>CAA): c.437 G>A in exon 6 of the COL5A2 gene (NM_000393.3) A variant of unknown significance has been identified in the COL5A2 gene. The R146Q variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The R146Q variant was not observed with any significance in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R146Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Additionally, this substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense mutations in nearby residues have not been indicating this region of the protein may be tolerant of change. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. This variant was found in TAAD.

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