Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000004452 | SCV000800662 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2I | 2018-02-20 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002512756 | SCV003443925 | uncertain significance | Walker-Warburg congenital muscular dystrophy | 2022-07-18 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 134 of the FKRP protein (p.Arg134Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with limb-girdle muscular dystrophy (PMID: 14647208). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 4231). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Arg134 amino acid residue in FKRP. Other variant(s) that disrupt this residue have been observed in individuals with FKRP-related conditions (PMID: 33200426), which suggests that this may be a clinically significant amino acid residue. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
OMIM | RCV000004452 | SCV000024625 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2I | 2003-12-01 | no assertion criteria provided | literature only |