ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1887C>T (p.Phe629=)

gnomAD frequency: 0.00006  dbSNP: rs751234870
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000859080 SCV000285021 benign Familial hypercholesterolemia 2024-12-04 criteria provided, single submitter clinical testing
Robarts Research Institute, Western University RCV000225826 SCV000484765 benign Hypercholesterolemia, familial, 1 2019-08-22 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000859080 SCV001347004 benign Familial hypercholesterolemia 2017-07-17 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001192513 SCV001360707 benign not specified 2019-03-04 criteria provided, single submitter clinical testing Variant summary: The variant, LDLR c.1887C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00052 in 277248 control chromosomes, predominantly at a frequency of 0.0042 within the Latino subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 3 fold of the estimated maximal expected allele frequency for a pathogenic variant in LDLR causing Familial Hypercholesterolemia phenotype (0.0013), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Latino origin. To our knowledge, no occurrence of c.1887C>T in individuals affected with Familial Hypercholesterolemia and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Ambry Genetics RCV002408957 SCV002723139 likely benign Cardiovascular phenotype 2018-12-13 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.
All of Us Research Program, National Institutes of Health RCV000225826 SCV004818463 benign Hypercholesterolemia, familial, 1 2024-02-05 criteria provided, single submitter clinical testing
Natera, Inc. RCV000859080 SCV001453899 benign Familial hypercholesterolemia 2020-06-25 no assertion criteria provided clinical testing

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