ClinVar Miner

Submissions for variant NM_024301.5(FKRP):c.946C>T (p.Pro316Ser)

gnomAD frequency: 0.00001  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
Eurofins Ntd Llc (ga) RCV000178358 SCV000230424 uncertain significance not provided 2015-04-20 criteria provided, single submitter clinical testing
Counsyl RCV000670956 SCV000795883 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2I 2017-11-21 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002517730 SCV003443261 likely pathogenic Walker-Warburg congenital muscular dystrophy 2023-09-26 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 316 of the FKRP protein (p.Pro316Ser). 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 missense change has been observed in individuals with limb-girdle muscular dystrophy (PMID: 12666124, 34509255). ClinVar contains an entry for this variant (Variation ID: 197346). 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. 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. 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.
Baylor Genetics RCV003468865 SCV004197401 likely pathogenic Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5 2023-12-17 criteria provided, single submitter clinical testing

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