ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.547C>A (p.Arg183Ser)

dbSNP: rs757292254
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001191488 SCV001359310 uncertain significance Familial hypercholesterolemia 2023-03-08 criteria provided, single submitter clinical testing This missense variant (also known as p.Arg162Ser in the mature protein) replaces arginine with serine at codon 183 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 LDLR-related disorders in the literature. This variant has not been identified 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.
Fulgent Genetics, Fulgent Genetics RCV002484050 SCV002785547 uncertain significance Hypercholesterolemia, familial, 1 2022-04-05 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001191488 SCV003269634 uncertain significance Familial hypercholesterolemia 2021-09-24 criteria provided, single submitter clinical testing This sequence change replaces arginine with serine at codon 183 of the LDLR protein (p.Arg183Ser). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with LDLR-related conditions. ClinVar contains an entry for this variant (Variation ID: 927915). 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.
All of Us Research Program, National Institutes of Health RCV002484050 SCV004820179 uncertain significance Hypercholesterolemia, familial, 1 2023-09-04 criteria provided, single submitter clinical testing This missense variant (also known as p.Arg162Ser in the mature protein) replaces arginine with serine at codon 183 of the LDLR protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <=0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. 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 not been identified 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.

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