Submissions for variant NM_024301.5(FKRP):c.712_713del (p.Leu238fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002638812	SCV002976750	pathogenic	Walker-Warburg congenital muscular dystrophy	2023-10-09	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu238Aspfs*20) in the FKRP gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 258 amino acid(s) of the FKRP protein. This variant is not present in population databases (gnomAD no frequency). 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: 1934796). This variant disrupts a region of the FKRP protein in which other variant(s) (p.Leu452Cysfs*38) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV003464575	SCV004197425	likely pathogenic	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5	2023-06-01	criteria provided, single submitter	clinical testing