||Variant of uncertain status wrt Familial Hypercholesterolemia
||common in clinvar
rs137853964 represents two variants in the low density lipoprotein receptor LDLR gene; the first, known as c.2479G>T, p.Val827Phe or V827F, is considered by most submitters to ClinVar as likely to pathogenic for familial hypercholesterolemia. The second variant, known as c.2479G>A, p.Val827Ile or V827I, is more common and of uncertain status; on one check, 4 ClinVar sources said it was benign, 5 said it was of uncertain status, and 2 said it was likely to be pathogenic, so clearly, it is not clear.
This variant in the LDLR gene is reported as meeting at least one of three criteria considered pathogenic for familial hypercholesterolemia and therefore significantly higher risk of coronary artery disease in a sequencing based study of 26,000 participants.[PMID 27050191]
This SNP is being studied in participants in the NIH ClinSeq program.[PMID 19602640]
[PMID 15823] Beta-adrenergic stimulation of cyclic AMP content and parathyroid hormone release from isolated bovine parathyroid cells.
[PMID 10735632] Molecular genetic testing for familial hypercholesterolemia: spectrum of LDL receptor gene mutations in The Netherlands.
[PMID 15701167] Familial hypercholesterolemia in St-Petersburg: the known and novel mutations found in the low density lipoprotein receptor gene in Russia.
[PMID 18400033] Silent exonic mutations in the low-density lipoprotein receptor gene that cause familial hypercholesterolemia by affecting mRNA splicing.
[PMID 19026292] Longitudinal evaluation and assessment of cardiovascular disease in patients with homozygous familial hypercholesterolemia.
[PMID 19118540] Evaluation of high-resolution melting analysis for screening the LDL receptor gene.