ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.447T>C (p.Gly149=) (rs765386678)

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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 RCV000781508 SCV000919590 uncertain significance not specified 2018-12-11 criteria provided, single submitter clinical testing Variant summary: LDLR c.447T>C 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 1.6e-05 in 245972 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.447T>C has been reported in the literature in individuals affected with Familial Hypercholesterolemia (Zakharova_2005). These report(s) do not provide unequivocal conclusions about association of the variant with Familial Hypercholesterolemia. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as benign. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
LDLR-LOVD, British Heart Foundation RCV000238477 SCV000294717 benign Familial hypercholesterolemia 2016-03-25 criteria provided, single submitter literature only

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