Submissions for variant NM_001276270.2(MBD4):c.615dup (p.Asn206Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003551469	SCV004253589	pathogenic	not provided	2023-11-21	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Asn206*) in the MBD4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MBD4 are known to be pathogenic (PMID: 30049810, 35460607). This variant is present in population databases (rs769552413, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with MBD4-related conditions. For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences	RCV004757594	SCV005355524	uncertain significance	MBD4-related disorder	2024-03-05	no assertion criteria provided	clinical testing	The MBD4 c.615dupT variant is predicted to result in premature protein termination (p.Asn206*). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Loss of function has not been conclusively established as a mechanism for MBD4-related disorders. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.