ClinVar Miner

Submissions for variant NM_024301.5(FKRP):c.541C>A (p.Arg181Ser)

gnomAD frequency: 0.00006  dbSNP: rs777245868
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000634057 SCV000755335 uncertain significance Walker-Warburg congenital muscular dystrophy 2022-10-13 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 181 of the FKRP protein (p.Arg181Ser). This variant is present in population databases (rs777245868, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with FKRP-related conditions. ClinVar contains an entry for this variant (Variation ID: 528815). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
GeneDx RCV001591411 SCV001825235 uncertain significance not provided 2020-12-21 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); In silico analysis supports that this missense variant does not alter protein structure/function; Reported as heterozygous in an individual with autism and neuromuscular weakness; however, a second FKRP variant was not reported (Athey 2020)
Ambry Genetics RCV002343234 SCV002651575 uncertain significance Cardiovascular phenotype 2024-06-07 criteria provided, single submitter clinical testing The p.R181S variant (also known as c.541C>A), located in coding exon 1 of the FKRP gene, results from a C to A substitution at nucleotide position 541. The arginine at codon 181 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002492962 SCV002779877 uncertain significance Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1; Muscular dystrophy-dystroglycanopathy type B5; Autosomal recessive limb-girdle muscular dystrophy type 2I; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5 2021-11-22 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV001591411 SCV003832646 uncertain significance not provided 2020-09-14 criteria provided, single submitter clinical testing
Natera, Inc. RCV001275313 SCV001460337 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2I 2020-01-24 no assertion criteria provided clinical testing

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