Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory of Human Genetics, |
RCV000754837 | SCV000863547 | pathogenic | Nonsyndromic genetic hearing loss | criteria provided, single submitter | clinical testing | The c.2090T>G p.Leu697Trp variant in MYO3A gene has been described in two unrelated Brazilian families with autosomal dominant hearing loss. This variant segregated in 36 affected individuals form these two families. Functional studies revealed a decrease of function of the mutated protein, so that the elongation of stereocilia of cochlea hair cells is impaired when the mutant and wild type proteins are expressed together. Thus, a dominant negative effect of the mutated protein on the wild type protein has been characterized. | |
Laboratory of Human Genetics, |
RCV001269336 | SCV001446368 | pathogenic | nonsyndromic sensorineural hearing loss | 2020-11-24 | criteria provided, single submitter | research | We previously described (PMID: 29880844) the c.2090T>G (p.Leu697Trp; NM_017433.5; VCV000617675.1) variant in the MYO3A gene segregating with nonsyndromic late-onset progressive hearing loss in 36 affected subjects from two unrelated families (referred as Families 1 and 2 in this study Through functional studies, we demonstrated the dominant negative effect of this variant. Screening the variant in a collection of 101 Brazilian pedigrees presenting autosomal dominant nonsyndromic hearing loss revealed three additional familial cases of this variant, two from the Otorhinolaryngology Lab - LIM32 and one from Laboratory of Human Genetics, Institute of Biosciences - University of Sao Paulo. In addition, a Dutch family was also identified by Human Genetics - Radboudumc. The description of the four additional cases (3 from Brazil and 1 from The Netherlands) are at final revision for publishing in EJHG. |
Gene |
RCV001540164 | SCV001758018 | pathogenic | not provided | 2020-08-31 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate that L697W results in the displacement of wild-type protein, suggestive of a dominant negative effect (Dantas et al., 2018); Not observed in large population cohorts (Lek et al., 2016); 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: 29880844) |
OMIM | RCV003768264 | SCV004565399 | pathogenic | Deafness, autosomal dominant 90 | 2024-02-16 | no assertion criteria provided | literature only |