Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000778505 | SCV000914778 | uncertain significance | MKS1-related disorder | 2018-04-02 | criteria provided, single submitter | clinical testing | The MKS1 c.370C>T (p.Arg124Ter) variant is a stop-gained variant that is predicted to result in a premature termination of the protein. A literature search was performed for the gene, cDNA change, and amino acid change in relation to Bardet-Biedl syndrome or Meckel syndrome. No publications were found based on this search. This variant is not found in the 1000 Genomes Project, the Exome Sequencing Project, Exome Aggregation Consortium, or the Genome Aggregation Database. Based on the variant frequency, disease prevalence, disease penetrance, and inheritance mode, this variant could not be ruled out of causing disease. Due to the potential impact of stop-gained variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for MKS1-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Labcorp Genetics |
RCV001389425 | SCV001590787 | pathogenic | Familial aplasia of the vermis; Meckel-Gruber syndrome | 2023-08-30 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 631779). This premature translational stop signal has been observed in individual(s) with clinical features of MKS1-related conditions (PMID: 30902645). This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Arg124*) in the MKS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MKS1 are known to be pathogenic (PMID: 19466712, 24886560, 26490104). |
| Laboratory of Medical Genetics, |
RCV001729702 | SCV001976721 | pathogenic | Joubert syndrome 28 | 2021-10-01 | criteria provided, single submitter | clinical testing | PVS1, PM2, PP3 |
| Baylor Genetics | RCV003472305 | SCV004194950 | pathogenic | Bardet-Biedl syndrome 13 | 2023-12-26 | criteria provided, single submitter | clinical testing | |
| Center for Genomic Medicine, |
RCV003989601 | SCV004807231 | uncertain significance | Meckel syndrome, type 1 | 2024-03-26 | criteria provided, single submitter | clinical testing |