Submissions for variant NM_000488.4(SERPINC1):c.1060C>T (p.Arg354Cys)

gnomAD frequency: 0.00001  dbSNP: rs765761813

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000693135	SCV000820991	uncertain significance	Hereditary antithrombin deficiency	2018-05-22	criteria provided, single submitter	clinical testing	This variant is not present in population databases (ExAC no frequency). 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The cysteine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SERPINC1-related disease. This sequence change replaces arginine with cysteine at codon 354 of the SERPINC1 protein (p.Arg354Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine.