ClinVar Miner

Submissions for variant NM_000310.3(PPT1):c.529C>G (p.Gln177Glu) (rs386833650)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188719 SCV000242343 pathogenic not provided 2014-04-08 criteria provided, single submitter clinical testing p.Gln177Glu (CAG>GAG): c.529 C>G in exon 5 of the PPT1 gene (NM_000310.3). The Q177E missense mutation in the PPT1 gene has been reported previously in an individual with late-infantile neuronal ceroid lipofuscinosis who had a nonsense mutation on the opposite allele (Das et al., 1998). Functional studies demonstrated significantly reduced enzyme activity in the presence of the Q177E mutation (Das et al, 2001). Therefore, Q177E is considered a disease causing mutation in the PPT1 gene. The variant is found in EPILEPSY panel(s).
Invitae RCV000049609 SCV000762916 pathogenic Neuronal ceroid lipofuscinosis 1 2019-12-30 criteria provided, single submitter clinical testing This sequence change replaces glutamine with glutamic acid at codon 177 of the PPT1 protein (p.Gln177Glu). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and glutamic acid. This variant is present in population databases (rs386833650, ExAC 0.007%). This variant has been reported in combination with another PPT1 variant in several individuals affected with late onset neuronal ceroid lipofuscinoses (PMID: 9664077). ClinVar contains an entry for this variant (Variation ID: 56198). This variant has been reported to affect PPT1 protein function (PMID: 11440996). For these reasons, this variant has been classified as Pathogenic.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000188719 SCV000861264 pathogenic not provided 2018-05-30 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000049609 SCV000915409 pathogenic Neuronal ceroid lipofuscinosis 1 2017-04-28 criteria provided, single submitter clinical testing The PPT1 c.529C>G (p.Gln177Glu) missense variant has been reported in a compound heterozygous state in five unrelated individuals with neuronal ceroid lipofuscinosis (NCL) (Das et al. 1998; Waliany et al. 2000; Kousi et al. 2012). Three individuals were affected with late-infantile NCL with the age of onset not reported in the other two subjects. The p.Gln177Glu variant was absent from 60 controls subjects but is reported at a frequency of 0.00007 in the European (non-Finnish) population of the Exome Aggregation Consortium. An enzyme activity of 7.3% of normal was detected in COS cells transfected with the p.Gln177Glu variant, while enzyme levels of 1.08% that of control was detected in lymphoblasts from an individual carrying the p.Gln177Glu variant (Das et al. 2001). Furthermore, kinetic analysis on highly purified variant protein using Sf9 insect cells revealed that the p.Gln177Glu variant led to substrate binding defects compared to wild type (Das et al. 2001). Based on the evidence, the p.Gln177Glu variant is classified as pathogenic for autosomal recessive neuronal ceroid lipofuscinosis. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000049609 SCV000082016 probable-pathogenic Neuronal ceroid lipofuscinosis 1 no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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