Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Victorian Clinical Genetics Services, |
RCV002472157 | SCV002768615 | uncertain significance | Autosomal dominant nonsyndromic hearing loss 4A | 2020-05-21 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as VUS – 3B. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene, caused by both missense and NMD predicted variants (PMID:31231018, PMID:28221712). (N) 0104 - Dominant Negative is a mechanism of disease for this gene, causing peripheral neuropathy. This has only been reported for a single, recurring mutation (p.Arg941Leu) (PMID:31231018). (N) 0107 - This gene is known to be associated with autosomal dominant disease. (N) 0200 - Variant is predicted to result in a missense amino acid change from leucine to proline (exon 24). (N) 0251 - Variant is heterozygous. (N) 0301 - Variant is absent from gnomAD. (P) 0501 - Missense variant consistently predicted to be damaging by multiple in silico. (P) 0600 - Variant is located in an annotated domain or motif, the myosin tail domain (PDB, NCBI). (N) 0705 - No comparable variants have previous evidence for pathogenicity. (N) 0807 - Variant has not previously been reported in a clinical context. (N) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1208 – Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign |