ClinVar Miner

Submissions for variant NM_000310.3(PPT1):c.837G>C (p.Gln279His) (rs72937434)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000118048 SCV000171163 benign not specified 2012-03-02 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
PreventionGenetics,PreventionGenetics RCV000118048 SCV000303558 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001083646 SCV000357390 benign Neuronal ceroid lipofuscinosis 1 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae RCV001083646 SCV000561185 benign Neuronal ceroid lipofuscinosis 1 2020-12-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV000715954 SCV000846786 benign History of neurodevelopmental disorder 2016-01-08 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000118048 SCV001370561 benign not specified 2020-05-08 criteria provided, single submitter clinical testing Variant summary: PPT1 c.837G>C (p.Gln279His) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0075 in 282822 control chromosomes, predominantly at a frequency of 0.079 within the African or African-American subpopulation in the gnomAD database, including 68 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 108 fold of the estimated maximal expected allele frequency for a pathogenic variant in PPT1 causing Neuronal Ceroid-Lipofuscinosis (Batten Disease) phenotype (0.00073), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.837G>C in individuals affected with Neuronal Ceroid-Lipofuscinosis (Batten Disease) and no experimental evidence demonstrating its impact on protein function have been reported. Four ClinVar submitters (evaluation after 2014) cite the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Genetic Services Laboratory, University of Chicago RCV000118048 SCV000152375 likely benign not specified no assertion criteria provided clinical testing Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.
Mayo Clinic Laboratories, Mayo Clinic RCV000675768 SCV000801489 benign not provided 2017-08-30 no assertion criteria provided clinical testing
Natera, Inc. RCV001083646 SCV001464014 benign Neuronal ceroid lipofuscinosis 1 2020-09-16 no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000675768 SCV001808030 likely benign not provided no assertion criteria provided clinical testing

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