Submissions for variant NM_002474.3(MYH11):c.5330G>A (p.Arg1777His) (rs201754049)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Clinical Services Laboratory,Illumina	RCV000277615	SCV000395220	uncertain significance	Lissencephaly, Recessive	2016-06-14	criteria provided, single submitter	clinical testing
Invitae	RCV000699065	SCV000827760	uncertain significance	Aortic aneurysm, familial thoracic 4	2018-03-16	criteria provided, single submitter	clinical testing	This sequence change replaces arginine with histidine at codon 1784 of the MYH11 protein (p.Arg1784His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs201754049, ExAC 0.01%). This variant has not been reported in the literature in individuals with MYH11-related disease. ClinVar contains an entry for this variant (Variation ID: 318096). 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.