ClinVar Miner

Submissions for variant NM_000090.3(COL3A1):c.217G>C (p.Asp73His) (rs200246388)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000252739 SCV000319286 uncertain significance Cardiovascular phenotype 2018-08-16 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Illumina Clinical Services Laboratory,Illumina RCV000264796 SCV000425496 benign Ehlers-Danlos syndrome, type 4 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae RCV000264796 SCV000541783 likely benign Ehlers-Danlos syndrome, type 4 2019-12-31 criteria provided, single submitter clinical testing
GeneDx RCV000520803 SCV000620150 uncertain significance not provided 2018-03-22 criteria provided, single submitter clinical testing The D73H variant of uncertain significance in the COL3A1 gene has not been published as pathogenic or been reported as benign to our knowledge. The D73H 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. Moreover, in-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Nevertheless, the D73H variant does not affect a Glycine residue in a Gly-X-Y motif in the triple helical region of the COL3A1 gene, where the majority of pathogenic missense variants occur (Stenson et al., 2014; Symoens et al., 2012). Finally, this variant is observed in 24/30,778 (0.08%) South Asian alleles and 10/126,058 (0.08%) European (non-Finnish) alleles 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.
Color RCV000771273 SCV000903418 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2019-11-01 criteria provided, single submitter clinical testing

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