ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.46C>G (p.Leu16Val)

dbSNP: rs2077058105
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel RCV002505759 SCV002817133 uncertain significance Hypercholesterolemia, familial, 1 2022-08-29 reviewed by expert panel curation The NM_000527.5(LDLR):c.46C>G (p.Leu16Val) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes PM2 and BP4 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1016/j.gim.2021.09.012). The supporting evidence is as follows: PM2:This variant is absent from gnomAD (gnomAD v2.1.1.). So PM2 is met. BP4: REVEL= 0.145, it is below 0.50, splicing evaluation required. Functional data on splicing not available. A) not on limits B) it creates a GT score in MES: de novo donor = -18.93, authentic donor = 11.08 --- de novo score is <0.8. Variant is not predicted to alter splicing, so BP4 is met.
Color Diagnostics, LLC DBA Color Health RCV001177803 SCV001342074 uncertain significance Familial hypercholesterolemia 2023-06-14 criteria provided, single submitter clinical testing This missense variant (also known as p.Leu-5Val in the mature protein) replaces leucine with valine at codon 16 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.
All of Us Research Program, National Institutes of Health RCV002505759 SCV004820104 uncertain significance Hypercholesterolemia, familial, 1 2023-06-26 criteria provided, single submitter clinical testing This missense variant (also known as p.Leu-5Val in the mature protein) replaces leucine with valine at codon 16 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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