ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.632A>T (p.His211Leu) (rs879254603)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000587367 SCV000697244 uncertain significance not provided 2017-06-22 criteria provided, single submitter clinical testing Variant summary: The LDLR c.632A>T (p.His211Leu) variant involves the alteration of a conserved nucleotide, resulting in a missense change in one of the low-density lipoprotein (LDL) receptor class A repeats (InterPro). 3/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to non-functioning tool). This variant is absent from the large control database ExAC (0/120210 control chromosomes). The variant has been reported in one hypercholesterolemia patient without strong evidence for pathogenicity (Widhalm_JIMD_2007). Variants affecting the same codon, p.H211Y and p.H211D (also known as p.H190Y and p.H190D, respectively) have been reported in hypercholesterolemia patients, suggesting this residue is a mutation hotspot. LDLR crystal structure study suggested functional importance of codon H211(Rudenko_2002). Taken together, due to lack of clinical and functional data, this variant is currently classified as a VUS until more evidence becomes available.
LDLR-LOVD, British Heart Foundation RCV000238558 SCV000294836 likely pathogenic Familial hypercholesterolemia 2016-03-25 criteria provided, single submitter literature only

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