ClinVar Miner

Submissions for variant NM_213599.2(ANO5):c.817C>T (p.Leu273Phe) (rs772929002)

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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 RCV000724847 SCV000700861 uncertain significance not provided 2017-02-28 criteria provided, single submitter clinical testing
GeneDx RCV000520042 SCV000617768 uncertain significance not specified 2017-07-26 criteria provided, single submitter clinical testing The L273F variant in the ANO5 gene has been reported previously, along with the common c.191dupA founder mutation, in a male with Miyoshi type distal muscular myopathy with normal dysferlin analysis and fully ambulatory (Linseen et al., 2013). The L273F variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The L273F variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar 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 L273F as a variant of uncertain significance.
Invitae RCV000687526 SCV000815098 uncertain significance Gnathodiaphyseal dysplasia; Limb-girdle muscular dystrophy, type 2L 2018-02-02 criteria provided, single submitter clinical testing This sequence change replaces leucine with phenylalanine at codon 273 of the ANO5 protein (p.Leu273Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is present in population databases (rs772929002, ExAC 0.003%). This variant has been reported in an individual affected with Miyoshi myopathy (PMID: 23530687). ClinVar contains an entry for this variant (Variation ID: 449531). 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, 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.

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