ClinVar Miner

Submissions for variant NM_174936.4(PCSK9):c.1431C>T (p.Cys477_Ala478=)

gnomAD frequency: 0.00417  dbSNP: rs28362268
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001080375 SCV000555880 benign Hypercholesterolemia, autosomal dominant, 3 2021-12-11 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589036 SCV000699987 benign not provided 2016-08-12 criteria provided, single submitter clinical testing Variant summary: The PCSK9 c.1431C>T (p.Cys477Cys) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect multiple ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 192/120408 control chromosomes (3 homozygotes), predominantly observed in the African subpopulation at a frequency of 0.017144 (176/10266). This frequency is about 183 times the estimated maximal expected allele frequency of a pathogenic PCSK9 variant (0.0000938), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. Taken together, this variant is classified as benign.
Color Diagnostics, LLC DBA Color Health RCV000776072 SCV000910776 benign Familial hypercholesterolemia 2017-10-24 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000589036 SCV001134564 benign not provided 2019-03-21 criteria provided, single submitter clinical testing
Illumina Laboratory Services,Illumina RCV001080375 SCV001253984 likely benign Hypercholesterolemia, autosomal dominant, 3 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services,Illumina RCV001097683 SCV001253985 likely benign Hypobetalipoproteinemia 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx RCV000589036 SCV001892647 benign not provided 2019-01-08 criteria provided, single submitter clinical testing
Genetic Services Laboratory,University of Chicago RCV001821313 SCV002071581 likely benign not specified 2018-10-18 criteria provided, single submitter clinical testing

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