ClinVar Miner

Submissions for variant NM_000744.6(CHRNA4):c.1138A>G (p.Ser380Gly) (rs187372416)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000716369 SCV000847209 uncertain significance Seizures 2016-07-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
GeneDx RCV000493059 SCV000582753 uncertain significance not provided 2017-05-16 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CHRNA4 gene. The S380G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The S380G variant is observed in 11/7702 (0.14%) alleles from individuals of East Asian background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The S380G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved and in silico analysis predicts this variant likely does not alter the protein structure/function. Additionally, this amino acid substitution is not predicted to occur within the transmembrane region of the protein, where the vast majority of pathogenic missense variants have been identified in association with epilepsy (Steinlein et al., 2010). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.

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