Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000822337 | SCV000963135 | pathogenic | Walker-Warburg congenital muscular dystrophy | 2023-12-29 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Cys317Alafs*111) in the FKRP gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 179 amino acid(s) of the FKRP protein. 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 premature translational stop signal has been observed in individual(s) with limb girdle muscular dystrophy (PMID: 23800702, 27439679, 28931339). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 664273). This variant disrupts the p.Ala455 amino acid residue in FKRP. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 14652796, 15574464, 16368217, 18671187, 19955119, 23420653, 23894383). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Genome- |
RCV001580551 | SCV001810426 | pathogenic | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5 | 2021-07-22 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV001784454 | SCV002023719 | pathogenic | not provided | 2019-12-09 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002507441 | SCV002810924 | pathogenic | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1; Muscular dystrophy-dystroglycanopathy type B5; Autosomal recessive limb-girdle muscular dystrophy type 2I; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5 | 2022-01-13 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001784454 | SCV003837152 | pathogenic | not provided | 2023-02-09 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation, as the last 179 amino acids are replaced with 110 different amino acids, and other loss-of-function variants have been reported downstream in HGMD; This variant is associated with the following publications: (PMID: 30107846, 30003095, 28931339, 27439679, 17055682, 23800702, 21296577, 32576226, 33200426) |
Baylor Genetics | RCV001580551 | SCV004197407 | pathogenic | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5 | 2023-09-12 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001830816 | SCV002091324 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2I | 2020-07-21 | no assertion criteria provided | clinical testing |