Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| LDLR- |
RCV000238259 | SCV000295081 | likely benign | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
| Labcorp Genetics |
RCV002055015 | SCV002361757 | likely benign | Familial hypercholesterolemia | 2025-01-19 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002298555 | SCV002598648 | likely benign | not specified | 2024-09-04 | criteria provided, single submitter | clinical testing | Variant summary: LDLR c.940+16G>A alters a nucleotide located at a position not widely known to affect splicing. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00014 in 250436 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in LDLR causing Familial Hypercholesterolemia (0.00014 vs 0.0013), allowing no conclusion about variant significance. c.940+16G>A has been reported in the literature in individuals affected with Familial Hypercholesterolemia (e.g., Chmara_2010, Noto_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: 20145306, 35339733). ClinVar contains an entry for this variant (Variation ID: 251545). Based on the evidence outlined above, the variant was classified as likely benign. |
| Ambry Genetics | RCV003298313 | SCV004000124 | likely benign | Cardiovascular phenotype | 2023-04-12 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| ARUP Laboratories, |
RCV005230180 | SCV005879086 | likely benign | not provided | 2024-04-29 | criteria provided, single submitter | clinical testing |