Submissions for variant NM_174936.4(PCSK9):c.1227C>T (p.Ala409=)

gnomAD frequency: 0.00006  dbSNP: rs146924245

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000459724	SCV000555868	likely benign	Hypercholesterolemia, autosomal dominant, 3	2025-01-19	criteria provided, single submitter	clinical testing
Robarts Research Institute, Western University	RCV000660742	SCV000782973	likely benign	Hypercholesterolemia, familial, 1	2018-01-02	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000459724	SCV001255797	uncertain significance	Hypercholesterolemia, autosomal dominant, 3	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001099350	SCV001255798	uncertain significance	Hypobetalipoproteinemia	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Color Diagnostics, LLC DBA Color Health	RCV001186469	SCV001352903	likely benign	Familial hypercholesterolemia	2018-11-14	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002367582	SCV002663181	likely benign	Cardiovascular phenotype	2022-08-01	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.
CeGaT Center for Human Genetics Tuebingen	RCV003311821	SCV004009849	likely benign	not provided	2023-04-01	criteria provided, single submitter	clinical testing	PCSK9: BP4, BP7
All of Us Research Program, National Institutes of Health	RCV000459724	SCV004836653	likely benign	Hypercholesterolemia, autosomal dominant, 3	2024-01-11	criteria provided, single submitter	clinical testing
GENinCode PLC	RCV001186469	SCV005627225	likely benign	Familial hypercholesterolemia	2025-01-10	criteria provided, single submitter	clinical testing	This is a synonymous (silent) variant that is not predicted to impact splicing and occurs at a nucleotide which is not highly conserved. This variant has been classified as Likely Benign (BP4, BP7).