Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000634067 | SCV000755345 | pathogenic | Walker-Warburg congenital muscular dystrophy | 2023-11-05 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser385*) in the FKRP gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 111 amino acid(s) of the FKRP protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individuals with congenital muscular dystrophy and limb girdle muscular dystrophy (PMID: 11592034, 12666124, 12707425, 14742276). This variant is also known as Ser384*. ClinVar contains an entry for this variant (Variation ID: 4219). For these reasons, this variant has been classified as Pathogenic. |
| Revvity Omics, |
RCV003137491 | SCV003822059 | pathogenic | not provided | 2021-12-29 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV003352746 | SCV004075991 | pathogenic | Cardiovascular phenotype | 2023-08-18 | criteria provided, single submitter | clinical testing | The p.S385* pathogenic mutation (also known as c.1154C>A), located in coding exon 1 of the FKRP gene, results from a C to A substitution at nucleotide position 1154. This changes the amino acid from a serine to a stop codon within coding exon 1. This alteration occurs at the 3' terminus of theFKRP gene, is not expected to trigger nonsense-mediated mRNA decay, and impacts the last 111 amino acids (22%) of the protein. However, premature stop codons are typically deleterious in nature, a significant portion of the protein is affected, and the impacted region is critical for protein function (Ambry internal data). This mutation has been detected in the compound heterozygous state with other FKRP variants in individuals with congenital and limb-girdle muscular dystrophies (Brockington M et al. Am J Hum Genet. 2001 Dec;69(6):1198-209; Poppe M et al. Neurology. 2003 Apr;60(8):1246-51). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
| Baylor Genetics | RCV003460427 | SCV004197406 | pathogenic | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5 | 2023-09-12 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV002226439 | SCV000024613 | pathogenic | Muscular dystrophy-dystroglycanopathy (congenital without impaired intellectual development), type B, 5 | 2001-12-01 | no assertion criteria provided | literature only |