ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.638G>C (p.Ser213Thr) (rs879254604)

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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 RCV000237432 SCV000294837 likely benign Familial hypercholesterolemia 1 2016-03-25 criteria provided, single submitter literature only
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000454439 SCV000539521 uncertain significance not specified 2016-10-31 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: This variant is not present in ExAC. It was seen in one patient with FH. It is classified in ClinVar with 1 star as Likely Benign by The British Heart Foundation. The region is not conserved but no species have a Thr at this position.
Invitae RCV000237432 SCV000544655 uncertain significance Familial hypercholesterolemia 1 2016-10-21 criteria provided, single submitter clinical testing This sequence change replaces serine with threonine at codon 213 of the LDLR protein (p.Ser213Thr). The serine residue is highly conserved and there is a small physicochemical difference between serine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with either definite or probable familial hypercholesterolemia (PMID: 16389549). This variant is also known as p.Ser192Thr in the literature. ClinVar contains an entry for this variant (Variation ID: 251338). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. While it is absent from the population and reported in affected individuals, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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