Submissions for variant NM_174936.4(PCSK9):c.658-6G>T

dbSNP: rs745633457

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002524934	SCV003282214	uncertain significance	Hypercholesterolemia, autosomal dominant, 3	2024-11-06	criteria provided, single submitter	clinical testing	This sequence change falls in intron 4 of the PCSK9 gene. It does not directly change the encoded amino acid sequence of the PCSK9 protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 440717). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Color Diagnostics, LLC DBA Color Health	RCV003581680	SCV004358039	uncertain significance	Familial hypercholesterolemia	2023-11-22	criteria provided, single submitter	clinical testing	This variant causes a G to T nucleotide substitution at the -6 position of intron 4 of the PCSK9 gene. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with PCSK9-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Institute of Human Genetics, University of Leipzig Medical Center	RCV002524934	SCV005423792	uncertain significance	Hypercholesterolemia, autosomal dominant, 3	2024-11-12	criteria provided, single submitter	clinical testing	Criteria applied: PS4_SUP,PM2_SUP,PP3
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum	RCV000508845	SCV000606694	pathogenic	Hypocholesterolemia		no assertion criteria provided	research