ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.2171C>T (p.Thr724Ile)

dbSNP: rs879255154
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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 RCV000238120 SCV000295906 likely benign Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Color Diagnostics, LLC DBA Color Health RCV001804978 SCV002053091 uncertain significance Familial hypercholesterolemia 2021-04-13 criteria provided, single submitter clinical testing This missense variant (also known as p.Thr703Ile in the mature protein) replaces threonine with isoleucine at codon 724 of the LDLR protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with familial hypercholesterolemia in the literature. This variant has been identified in 2/251224 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Invitae RCV001804978 SCV002175403 uncertain significance Familial hypercholesterolemia 2021-12-18 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 724 of the LDLR protein (p.Thr724Ile). This variant is present in population databases (no rsID available, gnomAD 0.002%). This missense change has been observed in individual(s) with familial hypercholesterolemia (PMID: 23375686). ClinVar contains an entry for this variant (Variation ID: 252246). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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