Submissions for variant NM_000393.5(COL5A2):c.2981T>C (p.Ile994Thr) (rs1354785209)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000809188	SCV000949330	uncertain significance	Ehlers-Danlos syndrome, classic type	2018-12-03	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine with threonine at codon 994 of the COL5A2 protein (p.Ile994Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with clinical features of vascular Ehlers-Danlos syndrome (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
CeGaT Praxis fuer Humangenetik Tuebingen	RCV000997625	SCV001153240	uncertain significance	not provided	2017-05-01	criteria provided, single submitter	clinical testing