Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001082736 | SCV000644873 | likely benign | Hypercholesterolemia, autosomal dominant, 3 | 2024-02-01 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000589661 | SCV000700002 | benign | not provided | 2016-12-15 | criteria provided, single submitter | clinical testing | Variant summary: The PCSK9 c.757C>T (p.Leu253Phe) variant involves the alteration of a conserved nucleotide. 3/4 in silico tools predict a damaging outcome for this substitution (SNPs&GO not captured due to low reliability index). This variant was found in 31/118852 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.0030852 (31/10048). This frequency is about 33 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 reported to be associated with about a 30% reduction of LDL-C levels further supporting a non-disease causing impact. Taken together, this variant is classified as benign. |
Color Diagnostics, |
RCV000771324 | SCV000903591 | likely benign | Familial hypercholesterolemia | 2022-01-01 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002395411 | SCV002672273 | benign | Cardiovascular phenotype | 2022-08-30 | criteria provided, single submitter | clinical testing | This alteration is classified as 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. |