Submissions for variant NM_174936.4(PCSK9):c.299C>G (p.Ala100Gly)

dbSNP: rs1484569818

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001192064	SCV001360009	uncertain significance	Familial hypercholesterolemia	2023-07-17	criteria provided, single submitter	clinical testing	This missense variant replaces alanine with glycine at codon 100 of the PCSK9 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). 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 been identified in 1/251322 chromosomes 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.
Ambry Genetics	RCV002436762	SCV002750742	uncertain significance	Cardiovascular phenotype	2022-02-07	criteria provided, single submitter	clinical testing	The p.A100G variant (also known as c.299C>G), located in coding exon 2 of the PCSK9 gene, results from a C to G substitution at nucleotide position 299. The alanine at codon 100 is replaced by glycine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.