Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000459145 | SCV000548511 | likely 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 tryptophan, which is neutral and slightly polar, at codon 110 of the FKRP protein (p.Arg110Trp). This variant is present in population databases (rs758759348, gnomAD 0.1%). This missense change has been observed in individuals with clinical features of limb-girdle muscular dystrophy (PMID: 18036232, 25135358, 33200426; Invitae). ClinVar contains an entry for this variant (Variation ID: 408718). 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.Arg110 amino acid residue in FKRP. Other variant(s) that disrupt this residue have been observed in individuals with FKRP-related conditions (PMID: 16368217), which suggests that this may be a clinically significant amino acid residue. 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. |
Fulgent Genetics, |
RCV000765451 | SCV000896742 | 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 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Athena Diagnostics Inc | RCV000991999 | SCV001143935 | uncertain significance | not provided | 2022-08-02 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000991999 | SCV001985464 | uncertain significance | not provided | 2020-04-01 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 21296577, 18036232, 25135358) |
Ambry Genetics | RCV002446816 | SCV002611670 | uncertain significance | Cardiovascular phenotype | 2023-03-30 | criteria provided, single submitter | clinical testing | The p.R110W variant (also known as c.328C>T), located in coding exon 1 of the FKRP gene, results from a C to T substitution at nucleotide position 328. The arginine at codon 110 is replaced by tryptophan, an amino acid with dissimilar properties. This variant co-occurred with other FKRP variants in individuals reported to have limb-girdle muscular dystrophy phenotype; however, phase determination was not always clear and/or clinical details were limited (Kang PB et al. BMC Musculoskelet Disord, 2007 Nov;8:115; Song D et al. Clin Genet. 2021 Mar;99(3):384-395; Jensen SM et al. Neuromuscul Disord. 2023 Feb;33(2):119-132). 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, |
RCV000991999 | SCV003832613 | uncertain significance | not provided | 2023-01-11 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV003463910 | SCV004197394 | pathogenic | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5 | 2023-10-28 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001272539 | SCV001454630 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2I | 2020-09-16 | no assertion criteria provided | clinical testing |