Submissions for variant NM_000310.4(PPT1):c.904A>G (p.Ile302Val)

gnomAD frequency: 0.00091  dbSNP: rs146902902

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000435004	SCV000232942	uncertain significance	not provided	2015-03-10	criteria provided, single submitter	clinical testing
GeneDx	RCV000435004	SCV000242330	uncertain significance	not provided	2024-04-03	criteria provided, single submitter	clinical testing	Reported previously in the heterozygous state 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 (PMID: 27861786); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27861786)
Illumina Laboratory Services, Illumina	RCV000515384	SCV000357389	uncertain significance	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
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.
Fulgent Genetics, Fulgent Genetics	RCV000515384	SCV000611426	uncertain significance	Neuronal ceroid lipofuscinosis 1	2017-05-23	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000515384	SCV000640464	likely benign	Neuronal ceroid lipofuscinosis 1	2024-01-30	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002317064	SCV000851748	likely benign	Inborn genetic diseases	2018-08-31	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
Mayo Clinic Laboratories, Mayo Clinic	RCV000435004	SCV001713813	uncertain significance	not provided	2019-10-28	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000435004	SCV002062792	likely benign	not provided	2023-02-01	criteria provided, single submitter	clinical testing	PPT1: BS2
Revvity Omics, Revvity	RCV000515384	SCV004236475	uncertain significance	Neuronal ceroid lipofuscinosis 1	2023-11-17	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000515384	SCV000734025	likely benign	Neuronal ceroid lipofuscinosis 1		no assertion criteria provided	clinical testing
GenomeConnect, ClinGen	RCV000515384	SCV000986819	not provided	Neuronal ceroid lipofuscinosis 1		no assertion provided	phenotyping only	Variant interpretted as Uncertain significance and reported on 05/31/2018 by GTR ID 26957. 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.
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille	RCV001252358	SCV001428112	uncertain significance	Intellectual disability	2019-01-01	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000515384	SCV001460029	likely benign	Neuronal ceroid lipofuscinosis 1	2019-11-11	no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001706153	SCV001927033	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000435004	SCV001971345	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003955098	SCV004785186	likely benign	PPT1-related disorder	2022-04-25	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).