Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000583160 | SCV000690955 | uncertain significance | Hypercholesterolemia, familial, 1 | 2017-09-25 | criteria provided, single submitter | clinical testing | Variant of Uncertain Significance due to insufficient evidence: This variant is a missense variant located in the signal peptide domain of the PCSK9 protein. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein function. Computational splicing tools suggest that this variant may not impact the RNA splicing. To our knowledge, functional assays have not been performed for this variant. This variant has been reported in multiple Japanese individuals with FH (PMID 26374825, 27206942) but also reported to be a common polymorphism in Japan (PMID 14727156, 27206942). This variant has been identified in 7/1727 East Asian chromosomes in the Exome Aggregation Consortium (ExAC) general population database. |
| Color Diagnostics, |
RCV000771578 | SCV000904162 | likely benign | Familial hypercholesterolemia | 2018-04-27 | criteria provided, single submitter | clinical testing | Likely Benign based on current evidence: This missense variant is located in the signal peptide domain of the PCSK9 protein. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein function. Computational splicing tools suggest that this variant may not impact the RNA splicing. To our knowledge, functional assays have not been performed for this variant. This variant has been reported in multiple Japanese individuals with familial hypercholesterolemia (PMID: 26374825, 27206942) but also reported to be a common polymorphism in Japan (PMID: 14727156, 27206942). This variant has been identified in 24/12184 East Asian chromosomes (0.1969%) in the general population by the Genome Aggregation Database (gnomAD). This variant allele frequency is greater than expected for the disorder based on prevalence, penetrance, and genetic/allelic heterogeneity. Based on available evidence, this variant is classified as Likely Benign. |
| Labcorp Genetics |
RCV000867528 | SCV001008767 | likely benign | Hypercholesterolemia, autosomal dominant, 3 | 2025-01-23 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000867528 | SCV001253579 | uncertain significance | Hypercholesterolemia, autosomal dominant, 3 | 2019-05-29 | 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. |
| Ambry Genetics | RCV002431733 | SCV002742273 | likely benign | Cardiovascular phenotype | 2020-09-30 | 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. |