ClinVar Miner

Submissions for variant NM_000310.3(PPT1):c.904A>G (p.Ile302Val) (rs146902902)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000720864 SCV000851748 uncertain significance History of neurodevelopmental disorder 2017-05-30 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000435004 SCV000510906 uncertain significance not provided 2016-07-13 criteria provided, single submitter clinical testing Converted during submission to Uncertain significance.
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000515384 SCV000734025 likely benign Ceroid lipofuscinosis neuronal 1 no assertion criteria provided clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000435004 SCV000232942 uncertain significance not provided 2015-03-10 criteria provided, single submitter clinical testing
Fulgent Genetics RCV000515384 SCV000611426 uncertain significance Ceroid lipofuscinosis neuronal 1 2017-05-23 criteria provided, single submitter clinical testing
GeneDx RCV000435004 SCV000242330 uncertain significance not provided 2018-03-08 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the PPT1 gene. The I302V variant has been reported previously as a heterozygous variant in a male individual with hypsarrhythmia, infantile spasms, and developmental delay who also harbored a de novo pathogenic variant in KCNQ2 and a variant in PCDH19 (Millichap et al., 2016). The I302V variant is observed in 218/126,644 (0.17%) alleles from individuals of European background in large population cohorts (Lek et al., 2016). The I302V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Illumina Clinical Services Laboratory,Illumina RCV000286785 SCV000357389 uncertain significance Neuronal Ceroid-Lipofuscinosis, Recessive 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000515384 SCV000640464 uncertain significance Ceroid lipofuscinosis neuronal 1 2018-05-24 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 302 of the PPT1 protein (p.Ile302Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs146902902, ExAC 0.2%). This variant has not been reported in the literature in individuals with PPT1-related disease. ClinVar contains an entry for this variant (Variation ID: 199009). 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.