ClinVar Miner

Submissions for variant NM_000086.2(CLN3):c.1086C>G (p.Asp362Glu) (rs376907245)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187019 SCV000240592 uncertain significance not provided 2018-08-28 criteria provided, single submitter clinical testing p.Asp362Glu (GAC>GAG): c.1086 C>G in exon 15 of the CLN3 gene (NM_001042432.1). The D362E 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 6,500 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 D362E variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved across species, and in silico analysis predicts this variant likely does not alter the protein structure/function. 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).
Invitae RCV000226481 SCV000285808 uncertain significance Neuronal ceroid lipofuscinosis 2016-01-01 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glutamic acid at codon 362 of the CLN3 protein (p.Asp362Glu). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant is present in population databases (rs376907245, ExAC 0.03%) but has not been reported in the literature in individuals with a CLN3-related disease. ClinVar contains an entry for this variant (Variation ID: 205098). 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"). However, the glutamic acid amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. In summary, this is a rare missense change that is not predicted to affect protein function or cause disease. However, the evidence is insufficient at this time to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Illumina Clinical Services Laboratory,Illumina RCV000355271 SCV000396321 uncertain significance Neuronal Ceroid-Lipofuscinosis, Dominant/Recessive 2016-06-14 criteria provided, single submitter clinical testing

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