Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| LDLR- |
RCV000237337 | SCV000295059 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
| Laboratory of molecular diagnosis of dyslipidemias, |
RCV000237337 | SCV001653612 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2021-05-24 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV005238788 | SCV005886466 | likely pathogenic | Familial hypercholesterolemia | 2025-02-14 | criteria provided, single submitter | clinical testing | Variant summary: LDLR c.922G>A (p.Glu308Lys) results in a conservative amino acid change located in the Low-density lipoprotein receptor domain of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251216 control chromosomes. c.922G>A has been reported in the literature in heterozygous individuals affected with Hypercholesterolemia (examples: Lombardi_2006, vanderGraaf_2011, Semenova_2020, Shakhtshneider_2021, Timoshchenko_2023, Rejman_2023). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 36752612, 16792510, 34834584, 21382890 , 32423031, 38203485). ClinVar contains an entry for this variant (Variation ID: 251528). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000237337 | SCV000606270 | pathogenic | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research |