ClinVar Miner

Submissions for variant NM_001145809.2(MYH14):c.820A>G (p.Ile274Val) (rs200424400)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000155160 SCV000204846 uncertain significance not specified 2017-02-07 criteria provided, single submitter clinical testing The p.Ile274Val variant in MYH14 has been previously reported by our laboratory in 3 individuals with hearing loss. This variant has been identified in 0.1% (17 /16486) of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, ht tp://exac.broadinstitute.org; dbSNP rs200424400). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conservation analyses sugges t that the p.Ile274Val variant may impact the protein, though this information i s not predictive enough to determine pathogenicity. In summary, the clinical si gnificance of the p.Ile274Val variant is uncertain.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000733279 SCV000861325 uncertain significance not provided 2018-05-30 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000733279 SCV000884184 uncertain significance not provided 2017-08-25 criteria provided, single submitter clinical testing The p.Ile266Val variant (rs200424400) has not been reported in the medical literature, but it is classified as a variant of uncertain significance in ClinVar (Variant ID: 178412). It has also been previously identified by our laboratory in a 38 year old woman without reported symptoms of hearing loss, and is listed in the Genome Aggregation Database (gnomAD) browser with an overall frequency of 0.042% (identified in 116 out of 276,962 chromosomes). The isoleucine at codon 266 is highly conserved considering 7 species up to Cow (Alamut software v2.9), and computational analyses suggest that this variant effects the MYH14 protein structure/function (SIFT: damaging, PolyPhen2: possibly damaging, and Mutation Taster: disease causing). However, based on the available information, the clinical significance of the p.Ile266Val variant cannot be determined with certainty.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000733279 SCV001152001 likely benign not provided 2018-06-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001132998 SCV001292683 likely benign Deafness, autosomal dominant 4 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

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