ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.731C>G (p.Ser244Cys) (rs1208667598)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Health, Inc RCV001187125 SCV001353796 uncertain significance Familial hypercholesterolemia 2020-10-07 criteria provided, single submitter clinical testing This missense variant (also known as p.Ser223Cys in the mature protein) replaces serine with cysteine at codon 244 of the LDLR protein. Computational prediction tool is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with familial hypercholesterolemia in the literature. This variant has been identified in 1/31406 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 RCV001187125 SCV001413877 uncertain significance Familial hypercholesterolemia 2019-10-15 criteria provided, single submitter clinical testing This sequence change replaces serine with cysteine at codon 244 of the LDLR protein (p.Ser244Cys). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with LDLR-related disease. ClinVar contains an entry for this variant (Variation ID: 440599). 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: Possibly Damaging; Align-GVGD: Class C1). 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. 5
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000508755 SCV000606212 pathogenic Familial hypercholesterolemia 1 no assertion criteria provided research

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