Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000670245 | SCV000795076 | likely pathogenic | Bardet-Biedl syndrome 13; Meckel syndrome, type 1; Joubert syndrome 28 | 2017-10-26 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000701980 | SCV000830807 | pathogenic | Familial aplasia of the vermis; Meckel-Gruber syndrome | 2023-11-20 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu277*) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MKS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 554581). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002469247 | SCV002766405 | likely pathogenic | Meckel syndrome, type 1 | 2022-11-17 | criteria provided, single submitter | clinical testing | Variant summary: MKS1 c.829G>T (p.Glu277X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position are classified as pathogenic in ClinVar. The variant was absent in 249568 control chromosomes. To our knowledge, no occurrence of c.829G>T in individuals affected with Meckel Syndrome Type 1 and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Baylor Genetics | RCV003472123 | SCV004194926 | likely pathogenic | Bardet-Biedl syndrome 13 | 2023-10-06 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV004719933 | SCV005324895 | pathogenic | not provided | 2023-11-03 | criteria provided, single submitter | clinical testing | Nonsense 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); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 25525159, 21228398) |