Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
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, |
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 |