Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Department of Otolaryngology – Head & Neck Surgery, |
RCV001375434 | SCV001572011 | uncertain significance | Hearing impairment | 2021-04-12 | criteria provided, single submitter | clinical testing | PM2_Moderate, PP3_Supporting |
Gene |
RCV002464454 | SCV002758949 | uncertain significance | not provided | 2022-05-31 | criteria provided, single submitter | clinical testing | Identified in a patient with unilateral sensorineural hearing loss in published literature, interpreted as a variant of uncertain significance (Zazo Seco et al., 2017); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 28000701) |
Invitae | RCV002464454 | SCV003016210 | uncertain significance | not provided | 2022-09-23 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MYO6 protein function. ClinVar contains an entry for this variant (Variation ID: 1065090). This missense change has been observed in individual(s) with sensorineural hearing impairment (PMID: 28000701). This variant is present in population databases (rs573770611, gnomAD 0.01%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 91 of the MYO6 protein (p.Ala91Thr). |