ClinVar Miner

Submissions for variant NM_024301.5(FKRP):c.1141dup (p.Ala381fs)

dbSNP: rs754403441
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000672422 SCV000797526 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2I 2018-02-05 criteria provided, single submitter clinical testing
Invitae RCV000688076 SCV000815673 pathogenic Walker-Warburg congenital muscular dystrophy 2022-05-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ala381Glyfs*9) in the FKRP gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 115 amino acid(s) of the FKRP protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with limb girdle muscular dystrophy (PMID: 26436962). This variant is also known as c.1140_1141insG. ClinVar contains an entry for this variant (Variation ID: 556419). This variant disrupts a region of the FKRP protein in which other variant(s) (p.Ser385*) have been determined to be pathogenic (PMID: 11592034, 12666124, 12707425, 14742276). 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.
GeneDx RCV002282320 SCV002571193 likely pathogenic not provided 2022-02-17 criteria provided, single submitter clinical testing Observed with a second FKRP variant in multiple individuals described with limb-girdle muscular dystrophy, although it is not known if the second FKRP variant is on the opposite allele (in trans) or on the same allele (in cis) (Ghaoui R et al., 2015; Song D et al., 2021); Frameshift variant predicted to result in protein truncation, as the last 115 amino acids are replaced with 8 different amino acids, and other loss-of-function variants have been reported downstream in HGMD.; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 27439679, 26436962, 33200426)
Baylor Genetics RCV003459638 SCV004197445 pathogenic Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5 2022-11-11 criteria provided, single submitter clinical testing
Natera, Inc. RCV000672422 SCV002091336 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2I 2021-03-03 no assertion criteria provided clinical testing

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