ClinVar Miner

Submissions for variant NM_000086.2(CLN3):c.250C>A (p.His84Asn) (rs201329358)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724494 SCV000230988 uncertain significance not provided 2015-02-19 criteria provided, single submitter clinical testing
GeneDx RCV000724494 SCV000573068 uncertain significance not provided 2017-02-07 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CLN3 gene. The H84N variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The H84N variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The H84N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, this substitution occurs at a position that is not conserved. In silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000701562 SCV000830368 uncertain significance Neuronal ceroid lipofuscinosis 2018-03-13 criteria provided, single submitter clinical testing This sequence change replaces histidine with asparagine at codon 84 of the CLN3 protein (p.His84Asn). The histidine residue is weakly conserved and there is a small physicochemical difference between histidine and asparagine. This variant is present in population databases (rs201329358, ExAC 0.05%). This variant has not been reported in the literature in individuals with CLN3-related disease. ClinVar contains an entry for this variant (Variation ID: 197711). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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