Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000767071 | SCV000204015 | uncertain significance | not provided | 2022-08-26 | criteria provided, single submitter | clinical testing | The p.Glu216Val variant in MYO6 has been reported in homozygous state in one Pakistani individual with severe-to-profound hearing loss and was not identified in 540 ethnically matched chromosomes (Ahmed 2003). Although this information suggests a role for this variant, it is possible that the variant segregates with another 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 variant is uncertain. |
| Gene |
RCV000767071 | SCV000568841 | uncertain significance | not provided | 2024-08-05 | criteria provided, single submitter | clinical testing | Observed in homozygous state in a patient with congenital sensorineural hearing loss in the literature, however, this individual was not screened for variants in other genes associated with hearing loss (PMID: 12687499), and this variant was observed as homozygous in at least one individual in the general population (gnomAD); Published functional studies are inconclusive regarding the functional impact of this variant (PMID: 32143290); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31250571, 29224747, 30245029, 32143290, 39019031, 12687499) |
| Illumina Laboratory Services, |
RCV000009111 | SCV000916164 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 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 | Autosomal dominant nonsyndromic hearing loss 22 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000767071 | SCV003004083 | uncertain significance | not provided | 2020-07-22 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with valine at codon 216 of the MYO6 protein (p.Glu216Val). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and valine. This variant is present in population databases (rs121912559, ExAC 0.3%). This variant has been observed in individual(s) with autosomal recessive deafness (PMID: 12687499). ClinVar contains an entry for this variant (Variation ID: 8580). This variant has been reported to affect MYO6 protein function (PMID: 32143290). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| OMIM | RCV000009111 | SCV000029328 | pathogenic | Autosomal recessive nonsyndromic hearing loss 37 | 2003-05-01 | no assertion criteria provided | literature only |