ClinVar Miner

Submissions for variant NM_001278074.1(COL5A1):c.2564C>G (p.Pro855Arg) (rs150539264)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000199153 SCV000249806 uncertain significance not provided 2018-09-13 criteria provided, single submitter clinical testing The P855R variant of uncertain significance in the COL5A1 gene has not been published as pathogenic or been reported as benign to our knowledge. The P855R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Nevertheless, while the P855R variant occurs within the triple helical region of the COL5A1 gene, it does not affect a Glycine residue in a Gly-X-Y motif, where the majority of pathogenic missense variants occur (Stenson et al., 2014; Symoens et al., 2012). Finally, this variant is observed in 0.02%-0.09% alleles across ethnic groups, including one homozygous individual, in large population cohorts (Lek et al., 2016), indicating it may be a rare benign variant. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Ambry Genetics RCV000621501 SCV000738586 uncertain significance Cardiovascular phenotype 2017-06-23 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV001084568 SCV000756004 likely benign Ehlers-Danlos syndrome, classic type 2019-12-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001084568 SCV001329886 likely benign Ehlers-Danlos syndrome, classic type 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.

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