Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000692387 | SCV000820208 | uncertain significance | Walker-Warburg congenital muscular dystrophy | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine with isoleucine at codon 392 of the FKRP protein (p.Phe392Ile). The phenylalanine residue is moderately conserved and there is a small physicochemical difference between phenylalanine and isoleucine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with limb-girdle muscular dystrophy (PMID: 28688748). 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"). 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. |