ClinVar Miner

Submissions for variant NM_004086.3(COCH):c.1348A>G (p.Ile450Val) (rs139503327)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000215913 SCV000271590 benign not specified 2018-10-09 criteria provided, single submitter clinical testing The p.Ile450Val variant in COCH is classified as benign because it has been iden tified in 0.1% (149/126048) of European chromosomes by gnomAD (http://gnomad.bro Furthermore, isoleucine (Ile) at position 450 is not highly co nserved in mammals, and one mammal (platypus) carries a valine (Val), supporting that this change may be tolerated. ACMG/AMP Criteria applied: BA1, BP4.
Illumina Clinical Services Laboratory,Illumina RCV000341711 SCV000386510 likely benign Deafness, autosomal dominant 9 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.
Eurofins NTD, LLC RCV000215913 SCV000854855 benign not specified 2017-09-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000755936 SCV000883615 uncertain significance not provided 2017-09-05 criteria provided, single submitter clinical testing The p.Ile450Val variant (rs139503327) has not been reported in the medical literature, or gene specific variation databases but has been reported to ClinVar (Variation ID:228523). This variant is listed in the genome Aggregation Database (gnomAD) with an overall population frequency of 0.08 percent (identified on 244 out of 275,816 chromosomes including 2 homozygotes). The isoleucine at position 450 is highly conserved up to Zebrafish (considering 12 species) (Alamut v2.10.0) and computational analyses of the effects of the p.Ile450Val variant on protein structure and function provide conflicting results (SIFT: damaging, MutationTaster: disease causing, PolyPhen-2: benign). Altogether, there is not enough evidence to classify the p.Ile450Val variant with certainty.
Invitae RCV000755936 SCV001033204 benign not provided 2018-08-13 criteria provided, single submitter clinical testing
GeneDx RCV000755936 SCV001893194 benign not provided 2019-04-29 criteria provided, single submitter clinical testing

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