ClinVar Miner

Submissions for variant NM_024301.5(FKRP):c.731G>A (p.Arg244His)

gnomAD frequency: 0.00010  dbSNP: rs764641619
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 12
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000725201 SCV000334847 uncertain significance not provided 2017-07-10 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000457561 SCV000548508 likely benign Walker-Warburg congenital muscular dystrophy 2025-01-01 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000331999 SCV000594784 uncertain significance not specified 2016-06-30 criteria provided, single submitter clinical testing
GeneDx RCV000725201 SCV000617404 uncertain significance not provided 2021-02-13 criteria provided, single submitter clinical testing Immunohistochemical analysis noted a depletion of alpha-dystroglycan glycosylation and mildly reduced alpha-dystroglycan on muscle biopsy from the patient (Boito et al., 2007); In silico analysis supports that this missense variant does not alter protein structure/function; Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 16344347, 26990548, 17952692, 30564623)
Counsyl RCV000664793 SCV000788808 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2I 2016-12-16 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000725201 SCV001250132 pathogenic not provided 2017-09-01 criteria provided, single submitter clinical testing
Athena Diagnostics RCV000725201 SCV001475118 uncertain significance not provided 2019-11-12 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000331999 SCV002598949 uncertain significance not specified 2025-02-19 criteria provided, single submitter clinical testing Variant summary: FKRP c.731G>A (p.Arg244His) results in a non-conservative amino acid change located in the fukutin-related protein stem domain (IPR055105) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00035 in 57478 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in FKRP causing Autosomal recessive limb-girdle muscular dystrophy type 2I (0.00035 vs 0.011), allowing no conclusion about variant significance. c.731G>A has been reported in the literature in at least one homozygous individual affected with Autosomal recessive limb-girdle muscular dystrophy type 2I (e.g., Boito_2005, Boito_2007), without strong evidence for causality. These data indicate that the variant may be associated with disease. Muscle biopsy analysis of this homozygous patient showed conflicting results indicating that glycosylated alpha-dystroglycan levels were possibly (but not clearly) decreased vs. controls (Boito_2005, Boito_2007). The following publications have been ascertained in the context of this evaluation (PMID: 17952692, 16344347). ClinVar contains an entry for this variant (Variation ID: 283038). Based on the evidence outlined above, the variant was classified as uncertain significance.
Ambry Genetics RCV002379117 SCV002671039 uncertain significance Cardiovascular phenotype 2024-01-19 criteria provided, single submitter clinical testing The p.R244H variant (also known as c.731G>A), located in coding exon 1 of the FKRP gene, results from a G to A substitution at nucleotide position 731. The arginine at codon 244 is replaced by histidine, an amino acid with highly similar properties. This variant was reported in a homozygous individual with limb girdle muscular dystrophy, including myalgia, more affected lower limbs than upper, and no muscle hypertrophy; muscle biopsy results showed some reduction in glycosylated alpha-dystroglycan expression compared to controls (Boito CA et al. Arch. Neurol., 2005 Dec;62:1894-9; Boito CA et al. Virchows Arch., 2007 Dec;451:1047-55). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV000725201 SCV003832608 uncertain significance not provided 2023-11-30 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV005396872 SCV006057864 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 2023-04-17 criteria provided, single submitter research
Natera, Inc. RCV000664793 SCV001460339 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2I 2020-01-12 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.