ClinVar Miner

Submissions for variant NM_004999.4(MYO6):c.647A>T (p.Glu216Val) (rs121912559)

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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 RCV000154352 SCV000204015 uncertain significance not specified 2014-04-28 criteria provided, single submitter clinical testing The Glu216Val variant in MYO6 has been reported in homozygous state in one Pakis tani individual with severe-to-profound hearing loss and was not identified in 5 40 ethnically matched chromosomes (Ahmed 2003). Although this information sugges ts a role for this variant, it is possible that the variant segregates with anot her variant that is causative for the hearing loss. Additional evidence, such as screening for this variant in a large ethnically-matched control population and functional studies, is needed to assume pathogenicity. Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the Glu216Val v ariant is uncertain.
GeneDx RCV000767071 SCV000568841 uncertain significance not provided 2018-07-31 criteria provided, single submitter clinical testing The E216V variant in the MYO6 gene has been reported previously in the homozygous state in one individual with congenital sensorineural hearing loss, however it is unknown whether this individual was screened for variants in other genes associated with hearing loss (Ahmed et al., 2003). The E216V variant is observed in 51/15602 (0.3%) alleles from individuals of South Asian background, in the ExAC dataset (Lek et al., 2016). The E216V 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. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret E216V as a variant of uncertain significance.
Illumina Clinical Services Laboratory,Illumina RCV000009111 SCV000916164 uncertain significance Deafness, autosomal recessive 37 2016-10-27 criteria provided, single submitter clinical testing The MYO6 c.647A>T (p.Glu216Val) missense variant has been reported in at least one study in a homozygous state in one individual with hearing loss and in a heterozygous state in at least one unaffected family member (Ahmed et al. 2003). The p.Glu216Val variant was absent from 351 controls, but is reported at a frequency of 0.03398 in the Gujarati Indian in Houston, Texas population from the 1000 Genomes Project. This allele frequency is high but is consistent with the disease prevalence. Computational analyses of the p.Glu216Val variant by Butt et al. (2012) showed that the variant may affect protein stability and result in structural abnormalities that could affect binding properties. The evidence for this variant is limited. The p.Glu216Val variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for recessive nonsyndromic hearing loss. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Mendelics RCV000987740 SCV001137180 uncertain significance Deafness, autosomal dominant 22 2019-05-28 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000987740 SCV001327404 benign Deafness, autosomal dominant 22 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). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
OMIM RCV000009111 SCV000029328 pathogenic Deafness, autosomal recessive 37 2003-05-01 no assertion criteria provided literature only

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