Submissions for variant NM_015627.3(LDLRAP1):c.713G>A (p.Arg238Gln)

gnomAD frequency: 0.00236  dbSNP: rs148579379

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000644527	SCV000766226	likely benign	Hypercholesterolemia, familial, 4	2024-01-31	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001805775	SCV002050797	likely benign	not specified	2023-12-12	criteria provided, single submitter	clinical testing	Variant summary: LDLRAP1 c.713G>A (p.Arg238Gln) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00054 in 250684 control chromosomes, predominantly at a frequency of 0.0076 within the African or African-American subpopulation in the gnomAD database, including 3 homozygotes. To our knowledge, no occurrence of c.713G>A in individuals affected with Familial Hypercholesterolemia and no experimental evidence demonstrating its impact on protein function have been reported. Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Ambry Genetics	RCV002360591	SCV002665798	likely benign	Cardiovascular phenotype	2021-03-02	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000644527	SCV003799370	likely benign	Hypercholesterolemia, familial, 4	2022-09-14	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000644527	SCV004172546	likely benign	Hypercholesterolemia, familial, 4	2023-04-11	criteria provided, single submitter	clinical testing
GENinCode PLC	RCV000644527	SCV005077841	benign	Hypercholesterolemia, familial, 4	2023-05-07	criteria provided, single submitter	clinical testing