ClinVar Miner

Submissions for variant NM_024301.5(FKRP):c.926A>G (p.Tyr309Cys)

gnomAD frequency: 0.00001  dbSNP: rs104894679
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001851646 SCV002268930 likely pathogenic Walker-Warburg congenital muscular dystrophy 2023-08-22 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 309 of the FKRP protein (p.Tyr309Cys). This variant is present in population databases (rs104894679, gnomAD 0.002%). This missense change has been observed in individual(s) with congenital muscular dystrophy (PMID: 11071142, 11592034). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 4218). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FKRP protein function. Experimental studies have shown that this missense change affects FKRP function (PMID: 31268217). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Revvity Omics, Revvity RCV003144103 SCV003832620 uncertain significance not provided 2019-10-21 criteria provided, single submitter clinical testing
Baylor Genetics RCV003466806 SCV004197418 likely pathogenic Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5 2023-07-10 criteria provided, single submitter clinical testing
OMIM RCV002226438 SCV000024612 pathogenic Muscular dystrophy-dystroglycanopathy (congenital without impaired intellectual development), type B, 5 2001-12-01 no assertion criteria provided literature only

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