Submissions for variant NM_000237.3(LPL):c.1421C>G (p.Ser474Ter)

gnomAD frequency: 0.08934  dbSNP: rs328

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000385586	SCV000472760	benign	Hyperlipoproteinemia, type I	2018-03-06	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	RCV001511819	SCV001719123	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001511819	SCV001882177	benign	not provided	2018-09-17	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 33339817, 8839720, 33111339, 15049943, 28267856, 23050023, 26999119, 26975783, 24974629, 24603370, 28640651, 29687697, 29632382, 29083407, 27516387, 29083408, 27984852, 27535653, 24704550, 26934567, 27055971, 28008009, 2216713, 17029199, 15793775, 21162862, 21816453, 25525159, 24039871, 19148283, 17560523, 19034041, 19664517, 19556723, 18187430, 19368142, 23113749, 25579610, 24176758, 19367320, 19018513, 17291198, 10450862, 17555736, 22244040, 18922999, 19185650)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001804709	SCV002051164	benign	not specified	2021-12-16	criteria provided, single submitter	clinical testing	Variant summary: LPL c.1421C>G (p.Ser474X) results in a premature termination two codons before the normal termination codon. The variant allele was found at a frequency of 0.092 in 251182 control chromosomes in the gnomAD database, including 1212 homozygotes. The observed variant frequency is approximately 27-fold of the estimated maximal expected allele frequency for a pathogenic variant in LPL causing Familial Lipoprotein Lipase Deficiency phenotype (0.0034), strongly suggesting that the variant is benign. Three ClinVar submitters have assessed this variant since 2014: all have classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Ambry Genetics	RCV002390085	SCV002696626	benign	Cardiovascular phenotype	2018-12-03	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.
Fulgent Genetics, Fulgent Genetics	RCV002504735	SCV002802043	benign	Hyperlipidemia, familial combined, LPL related; Hyperlipoproteinemia, type I	2022-05-02	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003974788	SCV004787233	benign	LPL-related condition	2023-06-19	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
OMIM	RCV000001598	SCV000021754	benign	LIPOPROTEIN LIPASE POLYMORPHISM	1992-01-15	no assertion criteria provided	literature only