ClinVar Miner

Submissions for variant NM_024301.5(FKRP):c.946C>A (p.Pro316Thr)

dbSNP: rs28937901
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Revvity Omics, Revvity RCV003144104 SCV003833405 likely pathogenic not provided 2022-08-23 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003591621 SCV004298423 pathogenic Walker-Warburg congenital muscular dystrophy 2023-11-07 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 316 of the FKRP protein (p.Pro316Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal recessive muscular dystrophy-dystroglycanopathy (PMID: 12654965). This variant is also known as Pro315Thr. ClinVar contains an entry for this variant (Variation ID: 4224). 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 with a positive predictive value of 95%. Experimental studies have shown that this missense change affects FKRP function (PMID: 31268217). This variant disrupts the p.Pro316 amino acid residue in FKRP. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11592034, 11741828, 16368217, 25135358). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000004445 SCV000024618 pathogenic Muscular dystrophy-dystroglycanopathy type B5 2003-03-25 no assertion criteria provided literature only
Counsyl RCV000675047 SCV000800483 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2I 2017-12-29 flagged submission clinical testing

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