Submissions for variant NM_174936.4(PCSK9):c.452C>T (p.Ala151Val)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV003172698	SCV003867153	uncertain significance	Cardiovascular phenotype	2022-12-18	criteria provided, single submitter	clinical testing	The p.A151V variant (also known as c.452C>T), located in coding exon 3 of the PCSK9 gene, results from a C to T substitution at nucleotide position 452. The alanine at codon 151 is replaced by valine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health	RCV004808460	SCV005431372	uncertain significance	Hypercholesterolemia, autosomal dominant, 3	2024-06-09	criteria provided, single submitter	clinical testing	This missense variant replaces alanine with valine at codon 151 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 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.