ClinVar Miner

Submissions for variant NM_004999.4(MYO6):c.271G>A (p.Ala91Thr)

gnomAD frequency: 0.00013  dbSNP: rs573770611
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department of Otolaryngology – Head & Neck Surgery, Cochlear Implant Center RCV001375434 SCV001572011 uncertain significance Hearing impairment 2021-04-12 criteria provided, single submitter clinical testing PM2_Moderate, PP3_Supporting
GeneDx 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).

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