Submissions for variant NM_018328.4(MBD5):c.961A>G (p.Met321Val) (rs369869865)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000188075	SCV000241679	likely benign	not specified	2017-07-06	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV000694398	SCV000822842	uncertain significance	Mental retardation, autosomal dominant 1	2018-12-21	criteria provided, single submitter	clinical testing	This sequence change replaces methionine with valine at codon 321 of the MBD5 protein (p.Met321Val). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and valine. This variant is present in population databases (rs369869865, ExAC 0.006%). This variant has not been reported in the literature in individuals with MBD5-related disease. ClinVar contains an entry for this variant (Variation ID: 206065). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). 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.
Ambry Genetics	RCV000718132	SCV000848994	uncertain significance	History of neurodevelopmental disorder	2017-02-16	criteria provided, single submitter	clinical testing	Lines of evidence used in support of classification: Insufficient evidence