Submissions for variant NM_000237.3(LPL):c.678A>G (p.Pro226=)

dbSNP: rs558390128

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000267552	SCV000472755	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	RCV000589102	SCV000696014	benign	not provided	2017-06-07	criteria provided, single submitter	clinical testing	Variant summary: The LPL c.678A>G (p.Pro226Pro) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. 4/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE site of SF2/ASF. This variant was found in 300/121406 control chromosomes (6 homozygotes), predominantly observed in the South Asian subpopulation at a frequency of 0.01805 (298/16510). This frequency is about 5.4 times the estimated maximal expected allele frequency of a pathogenic LPL variant (0.0033541), suggesting this is likely a benign polymorphism found primarily in the populations of South Asian origin. The variant of interest has not been reported in affected individuals via publications. Taken together, this variant is classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000589102	SCV001060808	benign	not provided	2024-11-27	criteria provided, single submitter	clinical testing
GeneDx	RCV000589102	SCV001942155	benign	not provided	2021-04-26	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002365429	SCV002662494	likely benign	Cardiovascular phenotype	2022-02-21	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.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV005404539	SCV006066065	benign	not specified	2025-04-09	criteria provided, single submitter	clinical testing	BS1;BP6;BP7
Natera, Inc.	RCV000267552	SCV001454754	benign	Hyperlipoproteinemia, type I	2020-04-14	no assertion criteria provided	clinical testing