ClinVar Miner

Submissions for variant NM_000086.2(CLN3):c.49G>A (p.Glu17Lys) (rs386833726)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000505765 SCV000240591 uncertain significance not provided 2018-03-14 criteria provided, single submitter clinical testing The E17K variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The E17K variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The E17K 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, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000549781 SCV000628932 uncertain significance Neuronal ceroid lipofuscinosis 2018-12-28 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 17 of the CLN3 protein (p.Glu17Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs386833726, ExAC 0.009%). This variant has not been reported in the literature in individuals with CLN3-related disease. ClinVar contains an entry for this variant (Variation ID: 205097). 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: "Tolerated"; PolyPhen-2: "Possibly 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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