Submissions for variant NM_000130.5(F5):c.4589A>C (p.Glu1530Ala)

gnomAD frequency: 0.00140  dbSNP: rs6007

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV003762928	SCV001117372	likely benign	Congenital factor V deficiency	2024-01-30	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001100085	SCV001256586	benign	Thrombophilia due to activated protein C resistance	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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina	RCV001100087	SCV001256588	benign	Thrombophilia due to thrombin defect	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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina	RCV001080915	SCV001256589	uncertain significance	Factor V deficiency	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	RCV001100088	SCV001256590	uncertain significance	Budd-Chiari syndrome	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.
PreventionGenetics, part of Exact Sciences	RCV003396564	SCV004119133	uncertain significance	F5-related condition	2023-05-19	criteria provided, single submitter	clinical testing	The F5 c.4589A>C variant is predicted to result in the amino acid substitution p.Glu1530Ala. This variant (also known as E1502A) has been identified in screening cohort studies, but without any association to disease phenotypes (Vos 2005. PubMed ID: 16246256; Watanabe et al. 2002. PubMed ID: 11950065). This variant is reported in 0.33% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-169509739-T-G) which suggests this variant is likely to be benign. However at this time we interpret its clinical significance as uncertain due to the absence of conclusive functional and genetic evidence.