Submissions for variant NM_001110792.2(MECP2):c.1231C>T (p.Pro411Ser)

gnomAD frequency: 0.00003  dbSNP: rs797045691

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel	RCV002472371	SCV002769731	likely benign	Rett syndrome	2022-12-09	reviewed by expert panel	curation	The allele frequency of the p.Pro399Ser variant in MECP2 (NM_004992.3) is 0.01% in Latino/Admixed American sub population in gnomAD, which is high enough to meet the BS1 criteria based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BS1). The p.Pro399Ser variant is observed in 1 unaffected individual (internal database) (BS2_supporting). In summary, the p.Pro399Ser variant in MECP2 is classified as a Likely Benign based on the ACMG/AMP criteria (BS1, BS2_supporting).
Genetic Services Laboratory, University of Chicago	RCV000192988	SCV000247941	uncertain significance	not specified	2013-02-08	criteria provided, single submitter	clinical testing
Invitae	RCV001521814	SCV001731222	benign	Severe neonatal-onset encephalopathy with microcephaly	2023-03-14	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002336514	SCV002644133	uncertain significance	Inborn genetic diseases	2018-02-07	criteria provided, single submitter	clinical testing	The p.P399S variant (also known as c.1195C>T), located in coding exon 3 of the MECP2 gene, results from a C to T substitution at nucleotide position 1195. The proline at codon 399 is replaced by serine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and serine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.