Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000507261 | SCV000604418 | likely pathogenic | not specified | 2017-02-02 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001799672 | SCV002043833 | uncertain significance | not provided | 2021-06-21 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27535533, 31589614) |
| Labcorp Genetics |
RCV001799672 | SCV002125449 | pathogenic | not provided | 2023-09-25 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gly106Aspfs*3) in the MYO3A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYO3A are known to be pathogenic (PMID: 12032315, 23990876). This variant is present in population databases (rs777580042, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with MYO3A-related conditions. ClinVar contains an entry for this variant (Variation ID: 439958). For these reasons, this variant has been classified as Pathogenic. |
| Laboratory for Molecular Medicine, |
RCV004017654 | SCV004848845 | likely pathogenic | Rare genetic deafness | 2022-11-03 | criteria provided, single submitter | clinical testing | The p.Gly106AspfsX3 variant in MYO3A has not been reported in individuals with nonsyndromic hearing loss and was reported in ClinVar (Variation ID 439958). It has been identified in 5/3046 South Asian chromosomes by gnomAD (https://gnomad.broadinstitute.org/). This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 106 and leads to a premature termination codon 3 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the MYO3A gene is an established disease mechanism in autosomal recessive nonsyndromic hearing loss. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive nonsyndromic hearing loss. ACMG/AMP Criteria applied: PM2_supporting, PVS1. |