Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000644545 | SCV000766245 | likely benign | Hypercholesterolemia, autosomal dominant, 3 | 2024-08-18 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000775274 | SCV000909533 | likely benign | Familial hypercholesterolemia | 2017-12-11 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV001101244 | SCV001257838 | uncertain significance | Hypobetalipoproteinemia | 2017-05-02 | 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
| Illumina Laboratory Services, |
RCV000644545 | SCV001257839 | benign | Hypercholesterolemia, autosomal dominant, 3 | 2017-05-02 | 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001584485 | SCV001821377 | likely benign | not specified | 2021-08-23 | criteria provided, single submitter | clinical testing | Variant summary: PCSK9 c.791C>T (p.Thr264Ile) results in a non-conservative amino acid change located in the Proteinase K-like catalytic domain of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 9.7e-05 in 247838 control chromosomes, predominantly at a frequency of 0.0013 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 34.67 fold of the estimated maximal expected allele frequency for a pathogenic variant in PCSK9 causing Familial Hypercholesterolemia phenotype (3.8e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. c.791C>T has been reported in the literature in individuals affected with Familial Hypercholesterolemia, without strong evidence for causality (Ohta_2016, Hori_2019). 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. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Three classified the variant as likely benign/benign while one classified the variant as VUS. Based on the evidence outlined above, the variant was classified as likely benign. |
| Ambry Genetics | RCV002422331 | SCV002676535 | likely benign | Cardiovascular phenotype | 2019-09-14 | 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. |
| All of Us Research Program, |
RCV000644545 | SCV004838576 | likely benign | Hypercholesterolemia, autosomal dominant, 3 | 2023-11-30 | criteria provided, single submitter | clinical testing |