Submissions for variant NM_001378120.1(MBD5):c.2828A>G (p.Gln943Arg)

gnomAD frequency: 0.00001  dbSNP: rs377062993

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000188102	SCV000241708	uncertain significance	not provided	2014-02-24	criteria provided, single submitter	clinical testing	p.Gln943Arg (CAG>CGG): c.2828 A>G in exon 10 of the MBD5 gene (NM_018328.4) The Q943R variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The Q943R variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals; however, Arginine is observed at this position in a distantly related species. In silico analysis predicts this variant likely does not alter the protein structure/function. To our knowledge, only deletions and frameshift mutations in MBD5 have been published in association with epilepsy. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).
Fulgent Genetics, Fulgent Genetics	RCV000765518	SCV000896827	uncertain significance	Intellectual disability, autosomal dominant 1	2018-10-31	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000188102	SCV002063898	uncertain significance	not provided	2021-10-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000765518	SCV003025668	uncertain significance	Intellectual disability, autosomal dominant 1	2023-07-08	criteria provided, single submitter	clinical testing	Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MBD5 protein function. This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 943 of the MBD5 protein (p.Gln943Arg). This variant is present in population databases (rs377062993, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with MBD5-related conditions. ClinVar contains an entry for this variant (Variation ID: 206090). 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.