Total submissions: 12
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000725201 | SCV000334847 | uncertain significance | not provided | 2017-07-10 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000457561 | SCV000548508 | likely benign | Walker-Warburg congenital muscular dystrophy | 2025-01-01 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV000331999 | SCV000594784 | uncertain significance | not specified | 2016-06-30 | criteria provided, single submitter | clinical testing | |
Gene |
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 | |
Ce |
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, |
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, |
RCV000725201 | SCV003832608 | uncertain significance | not provided | 2023-11-30 | criteria provided, single submitter | clinical testing | |
Department of Pathology and Laboratory Medicine, |
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, |
RCV000664793 | SCV001460339 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2I | 2020-01-12 | no assertion criteria provided | clinical testing |