ClinVar Miner

Submissions for variant NM_024301.5(FKRP):c.1364C>A (p.Ala455Asp) (rs28937903)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000201040 SCV000255777 pathogenic Limb-girdle muscular dystrophy-dystroglycanopathy, type C5 2015-09-14 criteria provided, single submitter clinical testing
Invitae RCV000532707 SCV000630831 pathogenic Walker-Warburg congenital muscular dystrophy 2018-08-16 criteria provided, single submitter clinical testing This sequence change replaces alanine with aspartic acid at codon 455 of the FKRP protein (p.Ala455Asp). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and aspartic acid. This variant is not present in population databases (rs28937903, ExAC no frequency). This variant has been reported in the homozygous or compound heterozygous state in multiple individuals affected with congenital muscular dystrophy, limb-girdle muscular dystrophy and muscle-eye brain disease (PMID: 14652796, 18671187, 14652796, 23420653, 16368217, 23894383). ClinVar contains an entry for this variant (Variation ID: 4226). Experimental studies have shown that this variant leads to cellular mislocalization and degradation of the FKRP protein in vitro (PMID: 15574464). In addition, this variant recapitulates the disease phenotype in a zebrafish model system (PMID: 19955119). For these reasons, this variant has been classified as Pathogenic.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000597675 SCV000708114 pathogenic not provided 2017-04-28 criteria provided, single submitter clinical testing
OMIM RCV000004447 SCV000024620 pathogenic Congenital muscular dystrophy-dystroglycanopathy with mental retardation, type B5 2004-02-01 no assertion criteria provided literature only
Counsyl RCV000201040 SCV000796853 pathogenic Limb-girdle muscular dystrophy-dystroglycanopathy, type C5 2018-01-03 no assertion criteria provided clinical testing

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