Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000495899 | SCV002817155 | uncertain significance | Hypercholesterolemia, familial, 1 | 2022-10-28 | reviewed by expert panel | curation | The NM_000527.4(LDLR):c.-142C>G variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes PM2 and PP4 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. PP4: Variant meets PM2 and is identified in 1 case with definite FH based on DLCN criteria from U4M - Lille University & CHRU Lille, Université de Lille . So PP4 is met. |
U4M - |
RCV000495899 | SCV000583618 | pathogenic | Hypercholesterolemia, familial, 1 | 2017-03-30 | criteria provided, single submitter | clinical testing | ACMG Guidelines: Pathogenic (i) |
Color Diagnostics, |
RCV001179375 | SCV001344027 | uncertain significance | Familial hypercholesterolemia | 2019-06-13 | criteria provided, single submitter | clinical testing | This variant causes a single nucleotide change in the promoter region of the LDLR gene. 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. |
Invitae | RCV001179375 | SCV003462064 | uncertain significance | Familial hypercholesterolemia | 2022-09-11 | criteria provided, single submitter | clinical testing | This variant occurs in a non-coding region of the LDLR gene. It does not change the encoded amino acid sequence of the LDLR protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with clinical features of familial hypercholesterolemia (Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 430742). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. |