Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000527187 | SCV000630828 | pathogenic | Walker-Warburg congenital muscular dystrophy | 2023-07-27 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 367 of the FKRP protein (p.Ile367Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with a dystrophinopathy-like phenotype (PMID: 28112097; Invitae). 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: 459227). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt FKRP protein function. For these reasons, this variant has been classified as Pathogenic. |
Ce |
RCV001093245 | SCV001250136 | pathogenic | not provided | 2018-05-01 | criteria provided, single submitter | clinical testing |