Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000771579 | SCV000904163 | likely benign | Familial hypercholesterolemia | 2018-01-11 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002352281 | SCV002657571 | likely benign | Cardiovascular phenotype | 2022-06-09 | 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003235390 | SCV003934238 | likely benign | not specified | 2023-05-23 | criteria provided, single submitter | clinical testing | Variant summary: PCSK9 c.60_65delGCTGCT (p.Leu22_Leu23del) results in an in-frame deletion that is predicted to remove two Leucine amino acids from a stretch of nine consecutive Leucines. The variant allele was found at a frequency of 5.6e-05 in 161082 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. However, the variant is located to a low complexity region, where several similar in-frame deletion/ duplication variants are reported, therefore most likely represents a repeat length polymorphism. To our knowledge, no occurrence of c.60_65delGCTGCT in individuals affected with Familial Hypercholesterolemia and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign. |
| Labcorp Genetics |
RCV003605677 | SCV004521074 | uncertain significance | Hypercholesterolemia, autosomal dominant, 3 | 2023-12-07 | criteria provided, single submitter | clinical testing | This variant, c.60_65del, results in the deletion of 2 amino acid(s) of the PCSK9 protein (p.Leu22_Leu23del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs778382130, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with PCSK9-related conditions. ClinVar contains an entry for this variant (Variation ID: 627764). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |