ClinVar Miner

Submissions for variant NM_000086.2(CLN3):c.266G>A (p.Arg89Gln) (rs766287694)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187027 SCV000240600 uncertain significance not provided 2018-08-14 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CLN3 gene. The R89Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R89Q variant is not observedat a significant frequency in large population cohorts (Lek et al., 2016). The R89Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant isprobably damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000801221 SCV000940990 uncertain significance Neuronal ceroid lipofuscinosis 2018-12-20 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 89 of the CLN3 protein (p.Arg89Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs766287694, ExAC 0.02%). This variant has not been reported in the literature in individuals with CLN3-related conditions. ClinVar contains an entry for this variant (Variation ID: 205106). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or 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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