ClinVar Miner

Submissions for variant NM_213599.2(ANO5):c.1733T>C (p.Phe578Ser) (rs137854526)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ANO5 @LOVD RCV000128774 SCV000172415 not provided not provided no assertion provided not provided
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000128774 SCV000333294 pathogenic not provided 2017-01-03 criteria provided, single submitter clinical testing
Invitae RCV000405473 SCV000645878 likely pathogenic Limb-girdle muscular dystrophy, type 2L 2017-02-27 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with serine at codon 578 of the ANO5 protein (p.Phe578Ser). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and serine. This variant is present in population databases (rs137854526, ExAC 0.1%). This variant has been reported in the compound heterozygous state with a second AN05 variant in individuals affected with Miyoshi-type distal myopathy (MMD), limb-girdle muscular dystrophy (LGMD), dilated cardiomyopathy (DCM), and in individuals with elevated creatine kinase levels (PMID: 23670307, 21186264, 23041008, 25891276). ClinVar contains an entry for this variant (Variation ID: 140553). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change that has been reported in the compound heterozygous state in multiple individuals affected with ANO5-related disorders. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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