ClinVar Miner

Submissions for variant NM_024301.5(FKRP):c.941C>T (p.Thr314Met) (rs398124395)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000082183 SCV000196821 pathogenic not provided 2018-09-18 criteria provided, single submitter clinical testing The T314M pathogenic variant in the FKRP gene has been reported previously in the homozygous state in multiple individuals with limb girdle muscular dystrophy from several families of Saudi Arabian ancestry (Boyden et al., 2010; Monies et al., 2016). The T314M variant was not observed in approximately 5,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The T314M variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret T314M as a pathogenic variant.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000082183 SCV000230409 pathogenic not provided 2016-04-28 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000178344 SCV000255778 pathogenic Limb-girdle muscular dystrophy-dystroglycanopathy, type C5 2014-09-15 criteria provided, single submitter clinical testing
Institute of Human Genetics,Klinikum rechts der Isar RCV000178344 SCV000680237 pathogenic Limb-girdle muscular dystrophy-dystroglycanopathy, type C5 2017-11-08 criteria provided, single submitter clinical testing
Invitae RCV001050280 SCV001214379 pathogenic Walker-Warburg congenital muscular dystrophy 2019-03-26 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 314 of the FKRP protein (p.Thr314Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has been observed to be homozygous or in combination with another FKRP variant in several individuals and families affected with autosomal recessive limb-girdle muscular dystrophy and to segregate with disease in families (PMID: 20623375, 27439679, 27671536, 28454995). ClinVar contains an entry for this variant (Variation ID: 96115). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic.

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