ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1054T>A (p.Cys352Ser)

dbSNP: rs879254769
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000237443 SCV000295165 likely pathogenic Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge RCV000237443 SCV000322925 likely pathogenic Hypercholesterolemia, familial, 1 2016-03-01 criteria provided, single submitter research 0/190 non-FH alleles
Ambry Genetics RCV002411081 SCV002715425 likely pathogenic Cardiovascular phenotype 2017-05-24 criteria provided, single submitter clinical testing The p.C352S variant (also known as c.1054T>A), located in coding exon 7 of the LDLR gene, results from a T to A substitution at nucleotide position 1054. The cysteine at codon 352 is replaced by serine, an amino acid with dissimilar properties. This alteration has been detected in several familial hypercholesterolemia (FH) cohorts and segregates with disease in one small FH family (Chiou KR et al. Atherosclerosis. 2011;216:383-9; Saban-Ruiz J et al. Atherosclerosis. 2015;241:e115; Hu M et al. J. Atheroscler. Thromb. 2016;23:520-31; Medeiros AM et al. Genet. Med. 2016;18:316-24). A number of alterations in the same codon (p.C352Y, p.C352W, p.C352R, and p.C352F) have also been associated with FH (Hobbs HH et al. Hum. Mutat. 1992;1:445-66; Bertolini S et al. Arterioscler Thromb Vasc Biol. 1999;19(2)408-18; Widhalm K et al. J Inherit Metab Dis. 2007;30(2):239-47; Marduel M et al. Hum. Mutat. 2010;31(11):E1811-24). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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