Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Testing Center for Deafness, |
RCV001290158 | SCV001478215 | pathogenic | Waardenburg syndrome type 2A | 2019-01-01 | criteria provided, single submitter | clinical testing | |
Institute of Medical Genetics and Applied Genomics, |
RCV001543505 | SCV001762118 | pathogenic | not provided | 2021-06-17 | criteria provided, single submitter | clinical testing | |
INGEBI, |
RCV001544533 | SCV001763579 | pathogenic | Nonsyndromic genetic hearing loss | 2021-07-15 | criteria provided, single submitter | clinical testing | Based on ACMG/AMP guidelines and Hearing Loss Expert Panel specific criteria:The c.877 C>T (p.Arg293*) in MITF gene is absent from population database (gnomAD) meeting PM2. This variant is predicted to generate a premature stop codon (more than 10% of the protein lost) applying to PVS1_Strong. It was reported in a family case with WS2 (PMID: 28690485). Besides, a family with autosomal dominant non-syndromic hearing loss exhibited this variant segregating in 5 affected relatives applyring to PP1_Strong (Internal data:Laboratory of Physiology and Genetics of Hearing). Considering all this information together: PM2, PVS1_S and PP1_Strong the c.877 C>T variant is classified as Pathogenic |
Gene |
RCV001543505 | SCV002028588 | pathogenic | not provided | 2024-04-03 | criteria provided, single submitter | clinical testing | Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 127 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 28690485, 34997062, 31992338, 34142234) |
Labcorp Genetics |
RCV003770470 | SCV004569530 | pathogenic | Tietz syndrome; Waardenburg syndrome type 2A; Melanoma, cutaneous malignant, susceptibility to, 8 | 2024-01-08 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg293*) in the MITF gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MITF are known to be pathogenic (PMID: 8659547, 20127975). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with autosomal dominant MITF-related conditions (PMID: 28690485, 34142234, 34997062). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 995923). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Deafness Molecular Diagnostic Center, |
RCV001290158 | SCV001763631 | likely pathogenic | Waardenburg syndrome type 2A | no assertion criteria provided | case-control |