Submissions for variant NM_015627.3(LDLRAP1):c.712C>T (p.Arg238Trp)

gnomAD frequency: 0.03285  dbSNP: rs41291058

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000457447	SCV000357057	likely benign	Hypercholesterolemia, familial, 4	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
GeneDx	RCV000418201	SCV000521312	benign	not specified	2016-11-25	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000418201	SCV000539519	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: Frequency in ESP (all): 472/13006=3.6%
Labcorp Genetics (formerly Invitae), Labcorp	RCV000457447	SCV000556920	benign	Hypercholesterolemia, familial, 4	2025-02-04	criteria provided, single submitter	clinical testing
Phosphorus, Inc.	RCV000457447	SCV000679930	uncertain significance	Hypercholesterolemia, familial, 4	2017-08-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589168	SCV000699406	benign	not provided	2017-06-02	criteria provided, single submitter	clinical testing	Variant summary: The LDLRAP1 c.712C>T (p.Arg238Trp) variant involves the alteration of a non-conserved nucleotide. 3/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 4281/120134 control chromosomes (112 homozygotes) at a frequency of 0.0356352, which is approximately 45 times the estimated maximal expected allele frequency of a pathogenic LDLRAP1 variant (0.0007906), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. Taken together, this variant is classified as benign.
Genome-Nilou Lab	RCV000457447	SCV001737313	benign	Hypercholesterolemia, familial, 4	2021-06-10	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002374500	SCV002668348	benign	Cardiovascular phenotype	2017-12-05	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
GENinCode PLC	RCV000457447	SCV005068299	benign	Hypercholesterolemia, familial, 4	2022-06-30	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001277162	SCV001464007	benign	Familial hypercholesterolemia	2020-09-16	no assertion criteria provided	clinical testing