Submissions for variant NM_000237.3(LPL):c.435G>A (p.Glu145=)

gnomAD frequency: 0.05843  dbSNP: rs248

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000302825	SCV000472753	benign	Hyperlipoproteinemia, type I	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587704	SCV000696013	benign	not provided	2017-06-07	criteria provided, single submitter	clinical testing	Variant summary: The LPL c.435G>A (p.Glu145Glu) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. Mutation taster predicts it as a polymorphism. 5/5 splice prediction tools predict no significant impact on normal splicing. In addition, ESE finder predicts that this variant may not affect binding of ESE sites. This variant was found in 6226/121336 control chromosomes (201 homozygotes) at a frequency of 0.0513121, which is approximately 15 times the estimated maximal expected allele frequency of a pathogenic LPL variant (0.0033541), thus this variant is likely a benign polymorphism. This variant was found at an allele frequency higher in controls than in patients with Familial Combined Hyperlipidemia in one study (Gagne_1994) and in one hypertriglyceridemia patient who carried biallelic mutations in GPIHBP1 gene (Buonuomo_2015), both evidences supporting for benign outcome. One clinical diagnostic laboratory (via ClinVar) has classified this variant as likely benign. Taken together, this variant is classified as benign.
Invitae	RCV000587704	SCV001728888	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000587704	SCV001935584	benign	not provided	2018-10-26	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002328878	SCV002632238	benign	Cardiovascular phenotype	2018-12-11	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.
Natera, Inc.	RCV000302825	SCV001456336	benign	Hyperlipoproteinemia, type I	2020-09-16	no assertion criteria provided	clinical testing