Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000674783 | SCV000800180 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2I | 2018-05-23 | criteria provided, single submitter | clinical testing | |
| Eurofins Ntd Llc |
RCV000735132 | SCV000863332 | uncertain significance | not provided | 2018-09-12 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002343423 | SCV002645555 | likely pathogenic | Cardiovascular phenotype | 2022-03-15 | criteria provided, single submitter | clinical testing | The p.R339H variant (also known as c.1016G>A), located in coding exon 1 of the FKRP gene, results from a G to A substitution at nucleotide position 1016. The arginine at codon 339 is replaced by histidine, an amino acid with highly similar properties. This variant has been detected in the compound heterozygous state with a frameshift variant and a known pathogenic variant in FKRP in individuals reported to have muscular dystrophy phenotypes (Brockington M et al. Am J Hum Genet, 2001 Dec;69:1198-209; Carlson CR et al. Neurology, 2017 Dec;89:2374-2380; Sframeli M et al. Neuromuscul Disord, 2017 Sep;27:793-803; Murphy LB et al. Ann Clin Transl Neurol, 2020 05;7:757-766). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Invitae | RCV002531360 | SCV003298105 | likely pathogenic | Walker-Warburg congenital muscular dystrophy | 2023-09-12 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 339 of the FKRP protein (p.Arg339His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with congenital muscular dystrophy and/or limb-girdle muscular dystrophy (PMID: 14742276, 28688748). ClinVar contains an entry for this variant (Variation ID: 558504). 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) performed at Invitae indicates that this missense variant is expected to disrupt FKRP protein function. 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. |