ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1301C>T (p.Thr434Met) (rs745343524)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000237891 SCV000295354 likely benign Familial hypercholesterolemia 1 2016-03-25 criteria provided, single submitter literature only
Robarts Research Institute,Western University RCV000237891 SCV000484722 uncertain significance Familial hypercholesterolemia 1 2019-08-22 criteria provided, single submitter clinical testing
Invitae RCV001044362 SCV001208156 uncertain significance Familial hypercholesterolemia 2019-12-30 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 434 of the LDLR protein (p.Thr434Met). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs745343524, ExAC 0.006%). This variant has been observed in individual(s) with familial hypercholesterolemia (PMID: 11668627, 15015036, 23375686, 18325082). This variant is also known as T413M in the literature. ClinVar contains an entry for this variant (Variation ID: 251775). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Thr434 amino acid residue in LDLR. Other variant(s) that disrupt this residue have been observed in individuals with LDLR-related conditions (PMID: 10634824, 21868016, Invitae), which suggests that this may be a clinically significant amino acid residue. 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.
Color RCV001044362 SCV001347904 likely benign Familial hypercholesterolemia 2018-11-11 criteria provided, single submitter clinical testing
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000237891 SCV000606389 pathogenic Familial hypercholesterolemia 1 no assertion criteria provided research

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