ClinVar Miner

Submissions for variant NM_024301.5(FKRP):c.142del (p.Arg48fs) (rs1555738103)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000553071 SCV000630833 pathogenic Walker-Warburg congenital muscular dystrophy 2018-12-14 criteria provided, single submitter clinical testing This sequence change deletes 1 nucleotide from exon 4 of the FKRP mRNA (c.142delC), causing a frameshift at codon 48. This creates a premature translational stop signal in the last exon of the FKRP mRNA (p.Arg48Valfs*20). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt and/or delete the last 448 amino acids (~90%) of the FKRP protein. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with an FKRP-related disease. A different truncating mutation (p.Ser385*) has been determined to be pathogenic in a family affected with congenital muscular dystrophy (PMID: 11592034). In addition, a downstream missense substitution (p.Ala455Asp) has been reported to be deleterious in patients affected with congenital muscular dystrophy (PMID: 14652796, 22908982, 15574464). This suggests that deletion of this region of the FKRP protein is causative of disease. For these reasons, this variant has been classified as Pathogenic.

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