Submissions for variant NM_001110792.2(MECP2):c.1495T>C (p.Ter499Arg)

dbSNP: rs267608337

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV003314564	SCV004014722	likely pathogenic	Rett syndrome	2023-05-02	criteria provided, single submitter	clinical testing	The MECP2 c.1459T>C (p.Ter487ArgextTer27) variant causes a stop-loss that is predicted to result in in-frame elongation of the protein. This variant occurs in the last exon of the gene and may escape nonsense-mediated mRNA decay. This variant has been identified in a de novo state in a female with a phenotype consistent with Rett syndrome (PMID: 11469283). The p.Ter487ArgextTer27 variant is not observed in version 2.1.1 or version 3.1.2 of the Genome Aggregation Database. This variant was identified in a de novo state. Based on the available evidence, the c.1459T>C (p.Ter487ArgextTer27) variant is classified as likely pathogenic for Rett syndrome.
Centre for Population Genomics, CPG	RCV003314564	SCV005040742	likely pathogenic	Rett syndrome	2024-04-23	criteria provided, single submitter	curation	This variant has been collected from RettBASE and curated to current modified ACMG/AMP criteria. Based on the classification scheme defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders Specifications to the ACMG/AMP Variant Interpretation Guidelines VCEP 3.0, this variant is classified as likely pathogenic. At least the following criteria are met: Protein length changes due to stop-loss variant (PM4_Strong). This variant is absent from gnomAD (PM2_Supporting). This variant has been identified as a de novo occurrence in an individual with Rett syndrome without confirmation of paternity and maternity (PM6). PMID 11469283
RettBASE	RCV000133018	SCV000188005	not provided	not provided		no assertion provided	not provided