ClinVar Miner

Submissions for variant NM_001278074.1(COL5A1):c.514G>T (p.Val172Phe) (rs150147262)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000199784 SCV000249872 uncertain significance not provided 2018-12-18 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the COL5A1 gene. The V172F variant has not been published as pathogenic or been reported as benign to our knowledge. It has been observed both independently, and in conjunction with other variants, in multiple individuals referred for Marfan/TAAD genetic testing at GeneDx, although segregation data from these individuals is not sufficient to determine the pathogenicity of this variant. This substitution occurs at a position where only amino acids with similar properties to valine (V) are tolerated across species, and V172F is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, V172F does not affect a Glycine residue in a Gly-X-Y motif in the triple helical region of the COL5A1gene, where the majority of pathogenic missense variants occur (Stenson et al., 2014; Symoens et al., 2012). Furthermore, this variant has been observed in 39/65444 (0.06%) alleles from individuals of Non-Finnish European ancestry in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server).
Invitae RCV001085122 SCV000631540 likely benign Ehlers-Danlos syndrome, classic type 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000619401 SCV000738565 uncertain significance Cardiovascular phenotype 2018-06-08 criteria provided, single submitter clinical testing Insufficient evidence
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000659439 SCV000781253 likely benign Connective tissue disease 2016-11-01 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000199784 SCV001155816 uncertain significance not provided 2019-11-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001085122 SCV001329746 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.
Blueprint Genetics RCV000157144 SCV000206867 uncertain significance Aortic valve disorder; Familial thoracic aortic aneurysm and aortic dissection 2014-04-08 no assertion criteria provided clinical testing

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