ClinVar Miner

Submissions for variant NM_000086.2(CLN3):c.1003T>C (p.Ser335Pro) (rs1567257016)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000696983 SCV000825570 uncertain significance Neuronal ceroid lipofuscinosis 2017-06-06 criteria provided, single submitter clinical testing This sequence change replaces serine with proline at codon 335 of the CLN3 protein (p.Ser335Pro). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with a CLN3-related disease. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This missense change is located in an intracellular domain of the CLN3 protein where multiple previously reported CLN3 missense mutations are found (PMID: 19132115). These observations suggest that a previously unreported missense substitution within this region may affect protein function, but experiments have not been done to test this possibility. In summary, this variant has uncertain impact on CLN3 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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