ClinVar Miner

Submissions for variant NM_000090.3(COL3A1):c.2445T>G (p.Pro815=) (rs199727625)

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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 RCV000621995 SCV000738535 likely benign Cardiovascular phenotype 2017-03-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Synonymous alterations with insufficient evidence to classify as benign
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769572 SCV000900969 likely benign Thoracic aortic aneurysm and aortic dissection 2017-04-18 criteria provided, single submitter clinical testing
GeneDx RCV000424938 SCV000512693 benign not specified 2016-11-30 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Integrated Genetics/Laboratory Corporation of America RCV000424938 SCV000695367 likely benign not specified 2017-11-27 criteria provided, single submitter clinical testing Variant summary: The COL3A1 c.2445T>G (p.Pro815Pro) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 4/5 splice prediction tools predict significantly strengthening impact on a canonical splicing donor site and ESE finder predicts that this variant may affect ESE sites at the locus. However, these predictions have yet to be confirmed by functional studies. This variant was found in 57/277050 control chromosomes, predominantly observed in the Latino subpopulation at a frequency of 0.001628 (56/34406). This frequency significantly exceeds the estimated maximal expected allele frequency of a pathogenic COL3A1 variant (0.0000013), strongly suggesting this is likely a benign polymorphism found primarily in the populations of Latino origin. However, considering the gnomAD population cohort includes cardio patients, these frequencies need to be taken with caution. One clinical diagnostic laboratory classified this variant as uncertain significance, while another clinical diagnostic laboratory classified this variant benign, all without strong evidence for causality. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely benign.
Invitae RCV000458481 SCV000541784 uncertain significance Ehlers-Danlos syndrome, type 4 2017-08-08 criteria provided, single submitter clinical testing

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