ClinVar Miner

Submissions for variant NM_024301.5(FKRP):c.1003G>A (p.Ala335Thr)

gnomAD frequency: 0.00026  dbSNP: rs776947530
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000306773 SCV000335256 uncertain significance not provided 2015-09-08 criteria provided, single submitter clinical testing
Invitae RCV000797226 SCV000936775 uncertain significance Walker-Warburg congenital muscular dystrophy 2022-09-12 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 335 of the FKRP protein (p.Ala335Thr). This variant is present in population databases (rs776947530, gnomAD 0.06%). 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: 283265). 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 not 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 RCV000306773 SCV001756222 uncertain significance not provided 2023-03-23 criteria provided, single submitter clinical testing Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant does not alter 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)
Athena Diagnostics Inc RCV000306773 SCV001880665 uncertain significance not provided 2021-05-13 criteria provided, single submitter clinical testing
Ambry Genetics RCV002401982 SCV002708993 uncertain significance Cardiovascular phenotype 2021-09-10 criteria provided, single submitter clinical testing The p.A335T variant (also known as c.1003G>A), located in coding exon 1 of the FKRP gene, results from a G to A substitution at nucleotide position 1003. The alanine at codon 335 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and threonine 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 RCV002480010 SCV002778321 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 2021-08-09 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000306773 SCV003832630 uncertain significance not provided 2023-03-27 criteria provided, single submitter clinical testing
Natera, Inc. RCV001833326 SCV002091331 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2I 2019-10-28 no assertion criteria provided clinical testing

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