Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004585986 | SCV000699408 | uncertain significance | not specified | 2024-04-16 | criteria provided, single submitter | clinical testing | Variant summary: LDLRAP1 c.605C>A (p.Ser202Tyr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00084 in 1613942 control chromosomes in the gnomAD database, including 6 homozygotes. c.605C>A has been reported in the literature in multiple heterozygous individuals affected with or with clinical features of Familial Hypercholesterolemia, without strong evidence for causality, with frequent reporting as a VUS (e.g. Rubba_2017, Luirink_2019, Rieck_2020, Rimbert_2022). These reports do not provide unequivocal conclusions about association of the variant with Familial Hypercholesterolemia. 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: 25911074, 11326085, 30795984, 32770674, 35047021, 28353356). ClinVar contains an entry for this variant (Variation ID: 4776). Based on the evidence outlined above, the variant was classified as VUS-possibly benign. |
| Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV000005042 | SCV000987666 | uncertain significance | Hypercholesterolemia, familial, 4 | criteria provided, single submitter | clinical testing | ||
| Labcorp Genetics |
RCV000005042 | SCV001031361 | likely benign | Hypercholesterolemia, familial, 4 | 2019-12-31 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000005042 | SCV001259183 | benign | Hypercholesterolemia, familial, 4 | 2017-07-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. |
| Laboratory of molecular diagnosis of dyslipidemias, |
RCV000005042 | SCV001653675 | likely pathogenic | Hypercholesterolemia, familial, 4 | 2021-05-24 | criteria provided, single submitter | clinical testing | Identified at heterozygous status in a patient with clinical suspect of Familial Hypercholesterolemia without pathogenic variants in LDLR, APOB, PCSK9, APOE, STAP1, ABCG5, ABCG8, LIPA and other lipid-related genes by next-generation sequencing. Likely pathogenic if in trans with an additional LDLRAP1 variant; probably affecting cholesterol levels at heterozygous status. |
| OMIM | RCV000005042 | SCV000025218 | pathogenic | Hypercholesterolemia, familial, 4 | 2001-05-18 | no assertion criteria provided | literature only | |
| Natera, |
RCV001275174 | SCV001460019 | uncertain significance | Familial hypercholesterolemia | 2020-01-11 | no assertion criteria provided | clinical testing |