ClinVar Miner

Submissions for variant NM_174936.4(PCSK9):c.225T>C (p.Pro75=)

gnomAD frequency: 0.00191  dbSNP: rs146563151
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001086878 SCV000644870 benign Hypercholesterolemia, autosomal dominant, 3 2024-01-25 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000586453 SCV000699991 benign not provided 2017-02-23 criteria provided, single submitter clinical testing Variant summary: The c.225C>T (p.Pro75=) in PCSK9 gene is a synonymous change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect a normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in control population dataset of ExAC at a frequency of 0.0005568 (67/ 120328 chrs tested), predominantly in individuals of African descent (0.006325; 66/10276 chrs tested). The observed frequencies exceed the estimated maximal expected allele frequency of a pathogenic variant in PCSK9 gene (0.00009). The variant has not, to our knowledge, been reported in affected individuals via published reports or cited by a reputable database/clinical laboratory. Taking together, the variant was classified as Benign.
Color Diagnostics, LLC DBA Color Health RCV000776137 SCV000911124 benign Familial hypercholesterolemia 2018-01-22 criteria provided, single submitter clinical testing
GeneDx RCV000586453 SCV001790738 likely benign not provided 2021-02-26 criteria provided, single submitter clinical testing
Ambry Genetics RCV002448724 SCV002733378 likely benign Cardiovascular phenotype 2017-03-14 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, National Institutes of Health RCV001086878 SCV004844122 benign Hypercholesterolemia, autosomal dominant, 3 2024-02-05 criteria provided, single submitter clinical testing

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