Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000155733 | SCV000840523 | pathogenic | Nonsyndromic genetic hearing loss | 2023-01-24 | reviewed by expert panel | curation | The NM_004999.4:c.238C>T (p.Arg80Ter) variant in MYO6 is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 4 and is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). The highest population minor allele frequency in gnomAD v2.1.1 is 0.0008% (1/113330 alleles) in the European (non-Finnish) population, which is lower than the ClinGen Hearing Loss VCEP threshold (<=0.002%) for PM2_Supporting. This variant has been reported in 2 families with teenage onset progressive sensorineural hearing loss, both displaying an autosomal dominant pattern of inheritance (PS4_Supporting; PMID: 32143290, 33111345). The variant has been reported to segregate with hearing loss in 2 affected family members from 1 family (PP1; PMID:33111345). In summary, this variant meets the criteria to be classified as Pathogenic for autosomal dominant hearing loss, based on the ACMG/AMP criteria applied, as specified by the ClinGen Hearing Loss Variant Curation Expert Panel: (PVS1, PM2_Supporting, PS4_Supporting, PP1). (VCEP specifications version 2.0.0; December 21, 2022) |
Laboratory for Molecular Medicine, |
RCV000844712 | SCV000205443 | likely pathogenic | Rare genetic deafness | 2013-10-05 | criteria provided, single submitter | clinical testing | The Arg80X variant in MYO6 has not been reported in individuals with hearing los s or in large population studies. This nonsense variant leads to a premature ter mination codon at position 80, which is predicted to lead to a truncated or abse nt protein. Nonsense variants in the MYO6 gene have been reported as disease cau sing variants in families with hearing loss. In summary, this variant is likely pathogenic, though additional studies are required to fully establish its clinic al significance. |
Gene |
RCV000480356 | SCV000570574 | likely pathogenic | not provided | 2020-01-10 | criteria provided, single submitter | clinical testing | Reported as a variant identified in the Deafness Variation Database, however, no additional information was provided (Sampaio-Silva et al., 2018); Nonsense 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; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 29044474, 32143290, 33111345) |
ARUP Laboratories, |
RCV000507733 | SCV000604424 | likely pathogenic | not specified | 2017-01-26 | criteria provided, single submitter | clinical testing | |
Laboratory of Prof. |
RCV001004798 | SCV001164286 | pathogenic | Autosomal dominant nonsyndromic hearing loss 22 | 2018-05-07 | criteria provided, single submitter | research | Dominant, teenage onset, progressive moderate high tone NSHL |