ClinVar Miner

Submissions for variant NM_024301.5(FKRP):c.1427G>A (p.Gly476Glu)

gnomAD frequency: 0.00005  dbSNP: rs375326964
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001205826 SCV001377103 uncertain significance Walker-Warburg congenital muscular dystrophy 2022-10-13 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 476 of the FKRP protein (p.Gly476Glu). This variant is present in population databases (rs375326964, gnomAD 0.009%). 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: 936918). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt FKRP 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.
GeneDx RCV001574262 SCV001801053 uncertain significance not provided 2024-12-11 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are a common cause of disease and they are underrepresented in the general population; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27439679)
Ambry Genetics RCV002393463 SCV002702744 uncertain significance Cardiovascular phenotype 2023-10-19 criteria provided, single submitter clinical testing The p.G476E variant (also known as c.1427G>A), located in coding exon 1 of the FKRP gene, results from a G to A substitution at nucleotide position 1427. The glycine at codon 476 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002497700 SCV002804977 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 2021-08-13 criteria provided, single submitter clinical testing
Natera, Inc. RCV001833808 SCV002091353 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2I 2020-02-21 no assertion criteria provided clinical testing

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