Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV000237327 | SCV002817122 | uncertain significance | Hypercholesterolemia, familial, 1 | 2022-08-29 | reviewed by expert panel | curation | The NM_000527.5(LDLR):c.2407_2424dup (p.Cys803_Leu808dup) is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes PM2 and PM4 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 follow: PM2_Met : Absent from controls in GnomAD (gnomAD v2.1.1). PM4_Met : The variant is an in-frame insertion which consists of a duplication of 18 nucleotides in exon 17, resulting in the in-frame insertion of six amino acids at the end of the transmembrane domain of the receptor protein smaller than whole exon. The variant met PM2 code as absent from controls in Gnomad database PP4_Met: variant met PM2 and was found in PMID: 11810272 in one patient with definite FH by SB criteria |
| LDLR- |
RCV000237327 | SCV000295996 | uncertain significance | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
| Invitae | RCV002519854 | SCV003443172 | uncertain significance | Familial hypercholesterolemia | 2022-10-26 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). 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. Experimental studies have shown that this variant affects LDLR function (PMID: 26220972). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 252325). This variant is also known as duplication aa 782–787, ins 782-787. This variant has been observed in individual(s) with familial hypercholesterolemia (PMID: 10735632). This variant, c.2407_2424dup, results in the insertion of 6 amino acid(s) of the LDLR protein (p.Cys803_Leu808dup), but otherwise preserves the integrity of the reading frame. |
| Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000237327 | SCV000606645 | pathogenic | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research |