Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory of Genetics and Molecular Cardiology, |
RCV000497107 | SCV000588687 | uncertain significance | Hypercholesterolemia, familial, 1 | 2016-03-01 | criteria provided, single submitter | research | |
Labcorp Genetics |
RCV001080081 | SCV001001093 | likely benign | Hypercholesterolemia, autosomal dominant, 3 | 2024-01-02 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000860913 | SCV001134566 | benign | not provided | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV001099463 | SCV001255921 | uncertain significance | Hypobetalipoproteinemia | 2017-04-27 | 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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Illumina Laboratory Services, |
RCV001080081 | SCV001255922 | uncertain significance | Hypercholesterolemia, autosomal dominant, 3 | 2017-04-27 | 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). 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. |
Color Diagnostics, |
RCV001176520 | SCV001340533 | likely benign | Familial hypercholesterolemia | 2018-07-06 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002395199 | SCV002703285 | likely benign | Cardiovascular phenotype | 2020-11-17 | 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. |
New York Genome Center | RCV001080081 | SCV002764494 | uncertain significance | Hypercholesterolemia, autosomal dominant, 3 | 2021-12-17 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV004767306 | SCV005381552 | likely benign | not specified | 2024-08-02 | criteria provided, single submitter | clinical testing | Variant summary: PCSK9 c.1660C>G (p.Gln554Glu) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00018 in 156836 control chromosomes, predominantly at a frequency of 0.0025 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 3 fold of the estimated maximal expected allele frequency for a pathogenic variant in PCSK9 causing Familial Hypocholesterolemia phenotype (0.001). c.1660C>G has been reported in at-least two screens in ostensibly healthy populations (Kotowski_2006,Lange_2014). These report(s) do not provide unequivocal conclusions about association of the variant with Familial Hypocholesterolemia. At least one publication reports experimental evidence evaluating an impact on protein function. These results showed no damaging effect of this variant (Le_2015). The following publications have been ascertained in the context of this evaluation (PMID: 19191301, 17971861, 16465619, 24507775, 26195630, 18280815, 24808179, 18799458, 17461796, 20172854, 26269718, 23105118, 21943799). ClinVar contains an entry for this variant (Variation ID: 431558). Based on the evidence outlined above, the variant was classified as likely benign. |