Submissions for variant NM_001110792.2(MECP2):c.418C>A (p.Gln140Lys)

dbSNP: rs267608469

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001062759	SCV001227578	likely pathogenic	Severe neonatal-onset encephalopathy with microcephaly	2022-11-29	criteria provided, single submitter	clinical testing	In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Gln128 amino acid residue in MECP2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12966523, 15875198). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 expected to disrupt MECP2 protein function. ClinVar contains an entry for this variant (Variation ID: 857143). This missense change has been observed in individual(s) with MECP2-related disease (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 128 of the MECP2 protein (p.Gln128Lys).
CeGaT Center for Human Genetics Tuebingen	RCV004809012	SCV005434077	likely pathogenic	not provided	2024-11-01	criteria provided, single submitter	clinical testing	MECP2: PM1, PM2, PM5