ClinVar Miner

Submissions for variant NM_213599.2(ANO5):c.2698A>C (p.Met900Leu) (rs148293985)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000428732 SCV000692707 uncertain significance not provided 2017-10-31 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000428732 SCV000511658 uncertain significance not provided 2016-11-08 criteria provided, single submitter clinical testing Converted during submission to Uncertain significance.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000176340 SCV000227979 likely benign not specified 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000176340 SCV000521261 likely benign not specified 2017-06-30 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Genetic Services Laboratory, University of Chicago RCV000176340 SCV000593211 uncertain significance not specified 2016-05-05 criteria provided, single submitter clinical testing
Invitae RCV000533294 SCV000645916 uncertain significance Gnathodiaphyseal dysplasia; Limb-girdle muscular dystrophy, type 2L 2018-05-03 criteria provided, single submitter clinical testing This sequence change replaces methionine with leucine at codon 900 of the ANO5 protein (p.Met900Leu). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and leucine. This variant is present in population databases (rs148293985, ExAC 0.2%). This variant has been observed on the opposite chromosome (in trans) from a likely pathogenic variant in an individual affected with Limb girdle muscular dystrophy (LGMD) (PMID:23670307). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. This variant has also been reported in individual affected with LGMD in the heterozygous state (PMID:23606453). ClinVar contains an entry for this variant (Variation ID: 195706). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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