ClinVar Miner

Submissions for variant NM_000744.6(CHRNA4):c.1634C>T (p.Thr545Met) (rs121912282)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000186912 SCV000240483 likely benign not specified 2013-11-12 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.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000513088 SCV000335694 uncertain significance not provided 2015-09-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000513088 SCV000609048 uncertain significance not provided 2017-06-30 criteria provided, single submitter clinical testing
Invitae RCV000654320 SCV000776210 uncertain significance Autosomal dominant nocturnal frontal lobe epilepsy 2018-09-24 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 545 of the CHRNA4 protein (p.Thr545Met). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs121912282, ExAC 0.03%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with CHRNA4-related disease. ClinVar contains an entry for this variant (Variation ID: 98320). 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 methionine 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.
Psychiatry Genetics Yale University RCV000084610 SCV000116746 not provided Tobacco use disorder no assertion provided not provided

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