Submissions for variant NM_001110792.2(MECP2):c.516_517del (p.Gly173fs)

dbSNP: rs267608486

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000255199	SCV000322255	pathogenic	not provided	2016-04-11	criteria provided, single submitter	clinical testing	The c.480_481delTG pathogenic variant in the MECP2 gene has been reported previously using alternate nomenclature 480del2 in an individual with atypical Rett syndrome (Weaving et al., 2003). The c.480_481delTG variant causes a frameshift starting with codon Glycine 161, changes this amino acid to a Glutamic Acid residue, and creates a premature Stop codon at position 13 of the new reading frame, denoted p.Gly161GlufsX13. This variant is predicted to cause loss of normal protein function through protein truncation as the last 326 amino acids of the MECP2 protein are lost and replaced with 12 incorrect amino acids. The c.480_481delTG variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.480_481delTG as a pathogenic variant.
Centre for Population Genomics, CPG	RCV000133133	SCV005040713	likely pathogenic	Rett syndrome	2024-01-23	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: Predicted to result in loss of function, and LOF is a known mechanism of disease (PVS1). This variant is absent from gnomAD (PM2_Supporting).
RettBASE	RCV000133133	SCV000188125	pathogenic	Rett syndrome	2002-04-05	no assertion criteria provided	curation