ClinVar Miner

Submissions for variant NM_000086.2(CLN3):c.938T>C (p.Leu313Pro) (rs141816714)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000733906 SCV000566485 uncertain significance not provided 2017-07-13 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CLN3 gene. The L313P variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The L313P variant is observed in 4/10052 (0.04%) alleles from individuals of African background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The L313P variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Additionally, this substitution occurs at a position where amino acids with similar properties to Leucine are tolerated across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense variants in nearby residues have not been reported in the Human Gene Mutation Database in association with NCL (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000733906 SCV000862011 uncertain significance not provided 2018-06-25 criteria provided, single submitter clinical testing
Invitae RCV001064358 SCV001229255 uncertain significance Neuronal ceroid lipofuscinosis 2019-12-19 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 313 of the CLN3 protein (p.Leu313Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is present in population databases (rs141816714, ExAC 0.04%). This variant has not been reported in the literature in individuals with CLN3-related conditions. ClinVar contains an entry for this variant (Variation ID: 418994). 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: "Deleterious"; 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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