ClinVar Miner

Submissions for variant NM_000086.2(CLN3):c.616G>A (p.Gly206Ser) (rs370603922)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000224526 SCV000240614 uncertain significance not provided 2018-10-19 criteria provided, single submitter clinical testing p.Gly206Ser (GGC>AGC): c.616 G>A in exon 9 of the CLN3 gene (NM_001042432.1). The G206S variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The G206S variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry. The G206S 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 occurs at a position that is conserved across species. 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).
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000224526 SCV000280820 uncertain significance not provided 2016-04-18 criteria provided, single submitter clinical testing Converted during submission to Uncertain significance.
Invitae RCV000632693 SCV000753879 uncertain significance Neuronal ceroid lipofuscinosis 2018-12-21 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 206 of the CLN3 protein (p.Gly206Ser). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs370603922, ExAC 0.04%). This variant has not been reported in the literature in individuals with CLN3-related disease. ClinVar contains an entry for this variant (Variation ID: 205118). 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: "Probably 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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