Submissions for variant NM_001110792.2(MECP2):c.1138C>T (p.His380Tyr)

gnomAD frequency: 0.00003  dbSNP: rs781968415

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
New York Genome Center	RCV001784168	SCV002025713	uncertain significance	Rett syndrome	2020-04-30	criteria provided, single submitter	clinical testing	The heterozygous missense variant, p.His380Tyr, identified in MECP2 has not been reported in affected individuals in the literature. The variant has 0.00001 allele frequency in the gnomAD database (3 out of 200,607 heterozygous alleles, no hemizygous males) indicating it is an extremely rare allele. The variant affects an evolutionary conserved residue and is predicted deleterious by multiple in silico prediction tools. However, no functional studies have been performed to evaluate the impact of this variant on normal function of the MECP2 protein. Based on the current evidence, the p.His380Tyr variant in the MECP2 gene is assessed as variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003638811	SCV004521135	likely benign	Severe neonatal-onset encephalopathy with microcephaly	2024-05-07	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004536310	SCV004113491	uncertain significance	MECP2-related disorder	2024-07-05	no assertion criteria provided	clinical testing	The MECP2 c.1102C>T variant is predicted to result in the amino acid substitution p.His368Tyr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0055% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.