ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.2324T>C (p.Val775Ala) (rs780300776)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000800276 SCV000939981 uncertain significance Familial hypercholesterolemias 2018-09-05 criteria provided, single submitter clinical testing This sequence change replaces valine with alanine at codon 775 of the LDLR protein (p.Val775Ala). The valine residue is weakly conserved and there is a small physicochemical difference between valine and alanine. This variant is present in population databases (rs780300776, ExAC 0.004%). This variant has not been reported in the literature in individuals with LDLR-related disease. 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 alanine 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. 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.
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000508779 SCV000606633 benign Familial hypercholesterolemia no assertion criteria provided research

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