ClinVar Miner

Submissions for variant NM_024301.5(FKRP):c.823C>T (p.Arg275Cys) (rs1247934219)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000674695 SCV000800081 uncertain significance Limb-girdle muscular dystrophy-dystroglycanopathy, type C5 2018-05-30 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000596371 SCV000703201 likely pathogenic not provided 2016-11-02 criteria provided, single submitter clinical testing
Invitae RCV000810990 SCV000951233 likely pathogenic Walker-Warburg congenital muscular dystrophy 2018-10-25 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 275 of the FKRP protein (p.Arg275Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in individuals affected with autosomal recessive limb-girdle muscular dystrophy (LGMD) (PMID: 17055682, 23800702). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 498269). 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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