Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Victorian Clinical Genetics Services, |
RCV002470583 | SCV002768780 | pathogenic | Autosomal recessive nonsyndromic hearing loss 79 | 2019-08-28 | criteria provided, single submitter | clinical testing | A heterozygous duplication variant was identified, NM_001128228.2(TPRN):c.943dup in exon 1 of 4 of the TPRN gene. This duplication is predicted to cause a frameshift from amino acid position 315 introducing a stop codon 32 residues downstream, NP_001121700.2(TPRN):p.(Leu315Profs*32), resulting in loss of normal protein function through nonsense-mediated decay (NMD). The variant is present in the gnomAD population database at a frequency of 0.003% (3 heterozygotes, 0 homozygotes) in the non-Finnish European population. It is not present in other subpopulations in gnomAD. It has been previously reported in a compound heterozygous state in a patient with autosomal recessive non-syndromic hearing loss (Sloan-Heggen, C. et al. (2016)); and has been reported as pathogenic in the Deafness Variation Database (http://deafnessvariationdatabase.org/). Other variants predicted to cause NMD have been reported as pathogenic in individuals with autosomal recessive deafness 79 (ClinVar). Based on information available at the time of curation, this variant has been classified as PATHOGENIC. |
Labcorp Genetics |
RCV002569388 | SCV003441511 | pathogenic | not provided | 2021-12-26 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with deafness (PMID: 26969326). This variant is present in population databases (rs765756665, gnomAD 0.004%). This sequence change creates a premature translational stop signal (p.Leu315Profs*32) in the TPRN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TPRN are known to be pathogenic (PMID: 20170898, 20170899). |
Gene |
RCV002569388 | SCV003935674 | pathogenic | not provided | 2023-06-26 | 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; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 26969326) |