Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000668106 | SCV000792657 | likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2I | 2017-07-06 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001554930 | SCV001776266 | likely pathogenic | not provided | 2019-08-05 | criteria provided, single submitter | clinical testing | Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 153 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (Stenson et al., 2014); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 30003095) |
Invitae | RCV002530737 | SCV003443345 | pathogenic | Walker-Warburg congenital muscular dystrophy | 2022-07-19 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 552780). This premature translational stop signal has been observed in individual(s) with limb-girdle muscular dystrophy (PMID: 30003095, 34509255). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Glu343*) in the FKRP gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 153 amino acid(s) of the FKRP protein. This variant disrupts a region of the FKRP protein in which other variant(s) (p.Ile478Thr) have been determined to be pathogenic (PMID: 16476814, 18639457, 19299310). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |