ClinVar Miner

Submissions for variant NM_000093.5(COL5A1):c.487G>A (p.Gly163Ser)

gnomAD frequency: 0.00001  dbSNP: rs764543567
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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 RCV002242720 SCV001562124 likely benign Ehlers-Danlos syndrome, classic type, 1 2024-11-26 criteria provided, single submitter clinical testing
Ambry Genetics RCV002341776 SCV002635659 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2021-05-20 criteria provided, single submitter clinical testing The p.G163S variant (also known as c.487G>A), located in coding exon 3 of the COL5A1 gene, results from a G to A substitution at nucleotide position 487. The glycine at codon 163 is replaced by serine, an amino acid with similar properties. Internal structural analysis indicates that this alteration disrupts the characteristic G-X-Y motif of the triple helical domain in the COL5A1 protein and inserts a bulky side chain into a sterically-constrained region (Bella J et al. Science. 1994;266:75-81; Hohenester E et al. Proc. Natl. Acad. Sci.U.S.A. 2008;105:18273-7; Ambry internal data). Glycine substitutions in the triple helical domain of COL5A1 have been reported in association with classic Ehlers-Danlos syndrome (cEDS), but the number of affected individuals is limited and several other COL5A1 glycine substitutions in the triple helical domain (e.g., p.G1078A and p.G1414A) are too common for disease in population databases (Symoens S et al. Hum. Mutat., 2012 Oct;33:1485-93; Ritelli M et al. Orphanet J Rare Dis. 2013 Apr;8:58). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV004728676 SCV005334410 uncertain significance not provided 2024-03-21 criteria provided, single submitter clinical testing Identified in patients with sporadic aortic dissection and atrioventricular nodal reentry tachycardia (AVNRT) in published literature (PMID: 34041919, 32508047); Not located in the triple helical region, where the majority of pathogenic missense variants occur (PMID: 22696272; HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22696272, 32508047, 34041919)

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