ClinVar Miner

Submissions for variant NM_024301.5(FKRP):c.229C>T (p.Gln77Ter)

gnomAD frequency: 0.00004  dbSNP: rs1051900223
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001379447 SCV001577250 likely pathogenic Walker-Warburg congenital muscular dystrophy 2023-12-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln77*) in the FKRP gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 419 amino acid(s) of the FKRP protein. This variant is present in population databases (no rsID available, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with limb-girdle muscular dystrophy (PMID: 22983245). ClinVar contains an entry for this variant (Variation ID: 1068020). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Ambry Genetics RCV002447504 SCV002734831 pathogenic Cardiovascular phenotype 2020-03-03 criteria provided, single submitter clinical testing The p.Q77* pathogenic mutation (also known as c.229C>T), located in coding exon 1 of the FKRP gene, results from a C to T substitution at nucleotide position 229. This changes the amino acid from a glutamine to a stop codon within coding exon 1. This mutation was reportedly detected in a limb girdle muscular dystrophy cohort; however, clinical details were limited (Ryzhkova OP et al. Zh Nevrol Psikhiatr Im S S Korsakova, 2012;112:55-9). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Natera, Inc. RCV001826153 SCV002088939 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2I 2021-02-25 no assertion criteria provided clinical testing

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