Submissions for variant NM_015141.4(GPD1L):c.370A>G (p.Ile124Val)

gnomAD frequency: 0.00291  dbSNP: rs72552293

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000029945	SCV000050768	likely benign	SUDDEN INFANT DEATH SYNDROME	2013-06-24	criteria provided, single submitter	research
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000170920	SCV000052600	likely benign	not specified	2018-07-25	criteria provided, single submitter	clinical testing	Variant summary: GPD1L c.370A>G (p.Ile124Val) results in a conservative amino acid change located in the N-terminal of the Glycerol-3-phosphate dehydrogenase, NAD-dependent domain (IPR011128) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0029 in 277792 control chromosomes in the gnomAD database and publications, including 7 homozygotes. The observed variant frequency is approximately 289-fold of the estimated maximal expected allele frequency for a pathogenic variant in GPD1L causing Arrhythmia phenotype (1e-05), strongly suggesting that the variant is benign. The variant, c.370A>G, has been reported in the literature in individuals affected with SIDS, sudden death, and atrial fibrillation (VanNorstrand_2007, Skinner_2014, Husser_2017). These data do not allow any conclusion about variant significance. At least one publication reports experimental evidence evaluating an impact on protein function, however, does not allow convincing conclusions about the variant effect (VanNorstrand_2007). Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
GeneDx	RCV000203752	SCV000223478	likely benign	not provided	2019-07-23	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 22995991, 19606473, 29077258, 17967976, 24055113, 23465283, 21215473, 25395996, 25998140, 23295036, 24715918, 28837624, 30615648, 15140536, 31019283, 31043699, 30847666)
Invitae	RCV001081825	SCV000262445	benign	Brugada syndrome	2024-01-31	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000170920	SCV000539250	benign	not specified	2016-03-29	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC: 1.2% (82/6614) Finnish chromosomes
Ambry Genetics	RCV000620285	SCV000737734	likely benign	Cardiovascular phenotype	2018-10-09	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.
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV000000824	SCV000883145	likely benign	Brugada syndrome 2	2018-11-21	criteria provided, single submitter	clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852958	SCV000995707	likely benign	Hypertrophic cardiomyopathy	2018-03-12	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000203752	SCV001153827	uncertain significance	not provided	2018-12-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000000824	SCV001157163	benign	Brugada syndrome 2	2023-10-26	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV000000824	SCV001934251	uncertain significance	Brugada syndrome 2	2020-10-19	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003952333	SCV004774886	likely benign	GPD1L-related disorder	2023-12-11	criteria provided, single submitter	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).
OMIM	RCV000000824	SCV000020974	pathogenic	Brugada syndrome 2	2007-11-13	no assertion criteria provided	literature only
Blueprint Genetics	RCV000157243	SCV000206970	likely benign	Primary familial hypertrophic cardiomyopathy; Long QT syndrome	2014-11-04	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000203752	SCV001922519	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000203752	SCV001930037	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000203752	SCV001954138	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000203752	SCV001968706	likely benign	not provided		no assertion criteria provided	clinical testing