ClinVar Miner

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

gnomAD frequency: 0.00002  dbSNP: rs1247934219
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000596371 SCV000703201 likely pathogenic not provided 2016-11-02 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000810990 SCV000951233 pathogenic Walker-Warburg congenital muscular dystrophy 2024-01-08 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 275 of the FKRP protein (p.Arg275Cys). 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 missense change has been observed in individual(s) with limb-girdle muscular dystrophy (PMID: 17055682, 23800702, 30293248, 30816495, 34602496; 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: 498269). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FKRP protein function. This variant disrupts the p.Arg275 amino acid residue in FKRP. Other variant(s) that disrupt this residue have been observed in individuals with FKRP-related conditions (PMID: 17055682, 17351538, 19917824, 23800702), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV003459466 SCV004197416 likely pathogenic Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5 2024-01-16 criteria provided, single submitter clinical testing
Counsyl RCV000674695 SCV000800081 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2I 2018-05-30 flagged submission clinical testing
Natera, Inc. RCV000674695 SCV002091320 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2I 2020-10-22 no assertion criteria provided clinical testing

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