ClinVar Miner

Submissions for variant NM_213599.2(ANO5):c.1640G>A (p.Arg547Gln) (rs139618850)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000322343 SCV000333848 uncertain significance not provided 2015-08-04 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000778318 SCV000914504 uncertain significance ANO5-Related Disorders 2017-04-28 criteria provided, single submitter clinical testing The ANO5 c.1640G>A (p.Arg547Gln) variant has been reported in three studies in which it is found in a total of four individuals with ANO5-Related Disorders, including in a compound heterozygous state with a known pathogenic variant in two brothers, and in a heterozygous state without a second identified variant in two additional unrelated individuals (van der Kooi et al. 2013; Sarkozy et al. 2013; Savarese et al. 2015). The two heterozygous individuals identified with this variant had a clinical suspicion of limb girdle muscualr dystrophy or nonspecific myopathic features, but no definitive clinical diagnoses (Sarkozy et al. 2013; Savarese et al. 2015). The p.Arg547Gln variant was absent from 52 controls (Savarese et al. 2015), but is reported at a frequency of 0.00227 in the African population of the 1000 Genomes Project. The evidence for this variant is limited. The p.Arg547Gln variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for ANO5-Related Disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000807697 SCV000947763 uncertain significance Gnathodiaphyseal dysplasia; Limb-girdle muscular dystrophy, type 2L 2018-10-10 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 547 of the ANO5 protein (p.Arg547Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs139618850, ExAC 0.2%). This variant has been observed to segregate with autosomal recessive limb girdle muscular dystrophy in a family (PMID: 23607914). ClinVar contains an entry for this variant (Variation ID: 282394). 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"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Department of Rehabilitation Medicine, Incheon St. Mary’s Hospital,College of Medicine, The Catholic University of Korea RCV000758149 SCV000882765 affects Limb-girdle muscular dystrophy, type 2L; Miyoshi muscular dystrophy 3 2019-02-11 no assertion criteria provided research The proband has another variant, NM_213599.2: c.1158delT.

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