ClinVar Miner

Submissions for variant NM_000310.3(PPT1):c.329A>G (p.Asn110Ser) (rs142894102)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724058 SCV000228845 uncertain significance not provided 2014-08-22 criteria provided, single submitter clinical testing
GeneDx RCV000724058 SCV000242336 uncertain significance not provided 2018-07-23 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the PPT1 gene. The N110S variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The N110S 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). This substitution occurs at a position that is conserved across species. Missense variants in nearby residues (G108R, Y109D, G118D) have been reported in the Human Gene Mutation Database in association with neuronal ceroid lipofuscinosis (NCL) (Stenson et al., 2014), supporting the functional importance of this region of the protein. Additionally, in silico analysis predicts this variant is probably damaging to the protein structure/function. However, the N110S variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000625813 SCV000746371 uncertain significance Neuronal ceroid lipofuscinosis 1 2017-12-03 criteria provided, single submitter clinical testing
Invitae RCV000625813 SCV000818289 uncertain significance Neuronal ceroid lipofuscinosis 1 2018-11-08 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 110 of the PPT1 protein (p.Asn110Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs142894102, ExAC 0.07%). This variant has not been reported in the literature in individuals with PPT1-related disease. ClinVar contains an entry for this variant (Variation ID: 196249). 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"). 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.
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille RCV001252359 SCV001428113 uncertain significance Intellectual disability 2019-01-01 no assertion criteria provided clinical testing

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