ClinVar Miner

Submissions for variant NM_024301.5(FKRP):c.1192G>A (p.Val398Ile)

gnomAD frequency: 0.00001  dbSNP: rs1471167981
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001348079 SCV001542367 uncertain significance Walker-Warburg congenital muscular dystrophy 2022-04-26 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 398 of the FKRP protein (p.Val398Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FKRP-related conditions. ClinVar contains an entry for this variant (Variation ID: 1043904). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Ambry Genetics RCV002341726 SCV002642453 uncertain significance Cardiovascular phenotype 2019-06-19 criteria provided, single submitter clinical testing The p.V398I variant (also known as c.1192G>A), located in coding exon 1 of the FKRP gene, results from a G to A substitution at nucleotide position 1192. The valine at codon 398 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species; however, isoleucine is the reference amino acid in other 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 RCV002486424 SCV002787374 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 2021-07-28 criteria provided, single submitter clinical testing
Natera, Inc. RCV001831138 SCV002091341 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2I 2021-09-17 no assertion criteria provided clinical testing

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