ClinVar Miner

Submissions for variant NM_174936.4(PCSK9):c.1171C>A (p.His391Asn)

gnomAD frequency: 0.00086  dbSNP: rs146471967
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000586543 SCV000699983 uncertain significance not provided 2016-06-22 criteria provided, single submitter clinical testing Variant summary: The PCSK9 c.1171C>A (p.His391Asn) variant involves the alteration of a conserved nucleotide. 3/5 in silico tools predict a damaging outcome. This variant was found in 24/92630 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.0029644 (24/8096). This frequency is about 31 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. Moreover, the variant was identified in pts with hypocholesterolemia, mainly of African origin. However, from a study, LDL-C lowering effect was statistically insignificant (Kotowski_2006). There are no published functional studies for this variant. Based on existing evidence, this variant is not associated with hypercholesterolemia, and there is no sufficient evidence that it can cause hypocholesterolemia. Some publications suggested that this variant is loss of function mutation without providing conclusive evidence. Taken together, the variant was classified as possibly benign variant for Hypercholesterolemia phenotype.
Invitae RCV001078920 SCV000766243 likely benign Hypercholesterolemia, autosomal dominant, 3 2024-01-03 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000776499 SCV000912081 benign Familial hypercholesterolemia 2022-01-01 criteria provided, single submitter clinical testing
New York Genome Center RCV001078920 SCV002764292 uncertain significance Hypercholesterolemia, autosomal dominant, 3 2021-07-13 criteria provided, single submitter clinical testing

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