Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV002505781 | SCV002817138 | uncertain significance | Hypercholesterolemia, familial, 1 | 2022-08-29 | reviewed by expert panel | curation | The NM_000527.5(LDLR):c.239A>G (p.Asn80Ser)variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence code PM2, 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) BP4 - REVEL = 0.176. It is below 0.50. splicing evaluation required. Functional data not available A) not on limits B) variant is exonic and at least 50bp upstream from canonical donor site and creates AG MES scores: de novo variant = -2.32; canonical acceptor = 7.07. Ratio de novo variant/canonical donor = -2.32/7.07 --- de novo score is negative, so it is not used. Variant is not predicted to alter splicing. |
Color Diagnostics, |
RCV001183871 | SCV001349716 | uncertain significance | Familial hypercholesterolemia | 2023-12-05 | criteria provided, single submitter | clinical testing | This missense variant (also known as p.Asn59Ser in the mature protein) replaces asparagine with serine at codon 80 of the LDLR protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant 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). 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. |