Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV004017820 | SCV004848863 | pathogenic | Rare genetic deafness | 2022-11-03 | criteria provided, single submitter | clinical testing | The p.Arg1078ProfsX6 variant in TRIOBP has been reported in the homozygous state in 4 members of a consanguineous Pakistani kindred and in 3 families from India as well as in the compound heterozygous state (with another loss-of-function variant) in at least 1 individual with hearing loss (Abu Rayyan 2020 PMID: 32747562, Riazuddin 2006 PMID: 16385457, van Beeck Calkoen 2019 PMID: 31152317, Zazo Seco 2017 PMID: 28000701, Wesdorp 2017 PMID: 28089734). It has also been reported in ClinVar (Variation ID 1034395). This variant has been identified in 5/30350 European chromosomes by gnomAD (https://gnomad.broadinstitute.org). This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 1078 and leads to a premature termination codon 6 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the TRIOBP gene is an established disease mechanism in autosomal recessive hearing loss. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive hearing loss. ACMG/AMP Criteria applied: PM2_Supporting, PM3, PVS1. |
Gene |
RCV004719138 | SCV005324986 | pathogenic | not provided | 2024-02-27 | criteria provided, single submitter | clinical testing | Frameshift 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; This variant is associated with the following publications: (PMID: 32747562, 16385457, 31152317, 28000701, 28089734) |
OMIM | RCV001337107 | SCV000021717 | pathogenic | Autosomal recessive nonsyndromic hearing loss 28 | 2006-01-01 | no assertion criteria provided | literature only |