Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000821581 | SCV000962343 | uncertain significance | Walker-Warburg congenital muscular dystrophy | 2022-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 23 of the FKRP protein (p.Tyr23Cys). This variant is present in population databases (rs201951207, gnomAD 0.03%). 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: 663660). 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 not expected to disrupt FKRP 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. |
Ambry Genetics | RCV002363165 | SCV002662964 | uncertain significance | Cardiovascular phenotype | 2023-03-24 | criteria provided, single submitter | clinical testing | The p.Y23C variant (also known as c.68A>G), located in coding exon 1 of the FKRP gene, results from an A to G substitution at nucleotide position 68. The tyrosine at codon 23 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly 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. |
Fulgent Genetics, |
RCV002495174 | SCV002790911 | 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 | 2022-01-10 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001825661 | SCV002088927 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2I | 2020-09-21 | no assertion criteria provided | clinical testing |