Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001065504 | SCV001230463 | uncertain significance | Walker-Warburg congenital muscular dystrophy | 2021-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan with arginine at codon 255 of the FKRP protein (p.Trp255Arg). The tryptophan residue is highly conserved and there is a moderate physicochemical difference between tryptophan and arginine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with FKRP-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 | RCV002393317 | SCV002670693 | uncertain significance | Cardiovascular phenotype | 2022-05-30 | criteria provided, single submitter | clinical testing | The p.W255R variant (also known as c.763T>A), located in coding exon 1 of the FKRP gene, results from a T to A substitution at nucleotide position 763. The tryptophan at codon 255 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. 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, |
RCV002479385 | SCV002782739 | 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 | 2021-09-21 | criteria provided, single submitter | clinical testing |