ClinVar Miner

Submissions for variant NM_017882.3(CLN6):c.4G>A (p.Glu2Lys) (rs796052360)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187117 SCV000240692 uncertain significance not provided 2014-09-25 criteria provided, single submitter clinical testing p.Glu2Lys (GAG>AAG): c.4 G>A in exon 1 of the CLN6 gene (NM_017882.2). The E2K variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 2,100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The E2K 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. This substitution alters a conserved position in the N-terminal domain of the CLN6 protein (Kousi et al., 2012), and missense mutations in nearby residues (R5W, R6T, A12T) have been reported in association with neuronal ceroid lipofuscinosis, supporting the functional importance of this region of the protein However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).

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