Submissions for variant NM_001110792.2(MECP2):c.490C>A (p.Pro164Thr)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002894195	SCV003235332	likely pathogenic	Severe neonatal-onset encephalopathy with microcephaly	2022-09-09	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with MECP2-related conditions. 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.Pro152 amino acid residue in MECP2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10767337, 10814718, 11055898, 11241840, 15173251, 21831886, 22923521, 23859859, 26418480, 27929079). 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. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 152 of the MECP2 protein (p.Pro152Thr).