ClinVar Miner

Submissions for variant NM_024301.5(FKRP):c.1027G>T (p.Glu343Ter)

dbSNP: rs587780334
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668106 SCV000792657 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2I 2017-07-06 criteria provided, single submitter clinical testing
GeneDx RCV001554930 SCV001776266 likely pathogenic not provided 2019-08-05 criteria provided, single submitter clinical testing Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 153 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (Stenson et al., 2014); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 30003095)
Invitae RCV002530737 SCV003443345 pathogenic Walker-Warburg congenital muscular dystrophy 2022-07-19 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 552780). This premature translational stop signal has been observed in individual(s) with limb-girdle muscular dystrophy (PMID: 30003095, 34509255). 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 sequence change creates a premature translational stop signal (p.Glu343*) in the FKRP gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 153 amino acid(s) of the FKRP protein. This variant disrupts a region of the FKRP protein in which other variant(s) (p.Ile478Thr) have been determined to be pathogenic (PMID: 16476814, 18639457, 19299310). 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.

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