ClinVar Miner

Submissions for variant NM_024301.5(FKRP):c.745G>A (p.Ala249Thr)

dbSNP: rs757955092
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001208376 SCV001379759 uncertain significance Walker-Warburg congenital muscular dystrophy 2024-01-28 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 249 of the FKRP protein (p.Ala249Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 939050). 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 with a negative predictive value of 95%. 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 RCV003145380 SCV003832636 uncertain significance not provided 2019-02-20 criteria provided, single submitter clinical testing
Ambry Genetics RCV004033726 SCV005028640 likely benign Cardiovascular phenotype 2023-11-03 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Natera, Inc. RCV001833831 SCV002088972 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2I 2020-04-18 no assertion criteria provided clinical testing

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