ClinVar Miner

Submissions for variant NM_018941.3(CLN8):c.50A>G (p.Asp17Gly) (rs148668081)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000717283 SCV000848132 uncertain significance Seizures 2016-11-01 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
GeneDx RCV000187135 SCV000240711 uncertain significance not provided 2017-07-31 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CLN8 gene. The D17G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The D17G 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 D17G 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 where amino acids with similar properties to Aspartic acid are tolerated across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
GenomeConnect, ClinGen RCV000509429 SCV000606932 not provided Ceroid lipofuscinosis neuronal 8 no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Invitae RCV000823172 SCV000964021 uncertain significance Neuronal ceroid lipofuscinosis 2018-12-10 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glycine at codon 17 of the CLN8 protein (p.Asp17Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is present in population databases (rs148668081, ExAC 0.08%). This variant has not been reported in the literature in individuals with CLN8-related disease. ClinVar contains an entry for this variant (Variation ID: 205201). 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: "Possibly 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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