ClinVar Miner

Submissions for variant NM_024301.5(FKRP):c.545A>G (p.Tyr182Cys) (rs543163491)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000336106 SCV000333605 pathogenic not provided 2016-10-07 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763055 SCV000893536 likely pathogenic Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1; Congenital muscular dystrophy-dystroglycanopathy (with or without mental retardation) type B5; Limb-girdle muscular dystrophy-dystroglycanopathy, type C5; Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies type A5 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000810074 SCV000950261 pathogenic Walker-Warburg congenital muscular dystrophy 2018-10-10 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 182 of the FKRP protein (p.Tyr182Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. While this variant is present in population databases (rs543163491), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed to segregate with autosomal recessive limb girdle muscular dystrophy (LGMD) in a family (PMID: 28931339). This variant has also been observed on the opposite chromosome (in trans) from other pathogenic variants or in combination with other FKRP variants in many individuals affected with LGMD (PMID: 27439679, 28931339, 14647208, 30003095, Invitae). These findings are consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 282247). 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: "Probably Damaging"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic.

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