ClinVar Miner

Submissions for variant NM_000093.4(COL5A1):c.4658C>T (p.Pro1553Leu) (rs530570306)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000620490 SCV000738643 uncertain significance Cardiovascular phenotype 2016-11-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
GeneDx RCV000199323 SCV000249843 uncertain significance not provided 2017-06-16 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the COL5A1 gene. The P1553L variant has not been published as pathogenic or been reported as benign to our knowledge. However, it has been identified independently in several unrelated individuals referred for Marfan/TAAD genetic testing at GeneDx. P1553L was observed in 4/16,512 (0.02%) alleles from individuals of South Asian ancestry in the Exome Aggregation Consortium (Lek et al., 2016). The P1553L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Moreover, this substitution occurs at a position that is conserved in mammals, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, although P1553L is located in the triple helical region of the COL5A1 gene, it does does not affect a Glycine residue in a Gly-X-Y motif, which is where the majority of pathogenic missense variants occur (Stenson et al., 2014; Symoens et al., 2012).
Invitae RCV000634652 SCV000755986 likely benign Ehlers-Danlos syndrome, classic type 2018-01-09 criteria provided, single submitter clinical testing

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