ClinVar Miner

Submissions for variant NM_024301.5(FKRP):c.1352C>T (p.Pro451Leu)

gnomAD frequency: 0.00001  dbSNP: rs886044542
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000343070 SCV000345344 uncertain significance not provided 2016-09-06 criteria provided, single submitter clinical testing
Ambry Genetics RCV002379155 SCV002693108 uncertain significance Cardiovascular phenotype 2021-08-06 criteria provided, single submitter clinical testing The p.P451L variant (also known as c.1352C>T), located in coding exon 1 of the FKRP gene, results from a C to T substitution at nucleotide position 1352. The proline at codon 451 is replaced by leucine, an amino acid with similar properties. This variant was reported as heterozygous in one individual from a limb-girdle muscular dystrophy (LGMD) cohort; however, clinical details were limited (Nallamilli BRR et al. Ann Clin Transl Neurol, 2018 Dec;5:1574-1587). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002487285 SCV002778165 uncertain significance Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1; Muscular dystrophy-dystroglycanopathy type B5; Autosomal recessive limb-girdle muscular dystrophy type 2I; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5 2022-02-17 criteria provided, single submitter clinical testing
Invitae RCV002518144 SCV003290563 uncertain significance Walker-Warburg congenital muscular dystrophy 2022-03-13 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 451 of the FKRP protein (p.Pro451Leu). This variant is present in population databases (no rsID available, gnomAD 0.01%). This missense change has been observed in individual(s) with limb-girdle muscular dystrophy (PMID: 30564623). ClinVar contains an entry for this variant (Variation ID: 290726). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Revvity Omics, Revvity RCV000343070 SCV003832605 uncertain significance not provided 2021-04-27 criteria provided, single submitter clinical testing

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