Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002222406 | SCV002500699 | uncertain significance | not specified | 2022-03-28 | criteria provided, single submitter | clinical testing | Variant summary: MECP2 c.308G>A (p.Gly103Asp) results in a non-conservative amino acid change located in the Methyl-CpG DNA binding domain (IPR001739) of the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 183390 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.308G>A in individuals affected with Rett Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Centre for Population Genomics, |
RCV000133060 | SCV004232217 | uncertain significance | Rett syndrome | 2024-01-15 | 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: Occurs in the well-characterized Methyl-DNA binding (MDB) functional domain of MECP2 (PM1). Computational prediction analysis tools suggests a deleterious impact (REVEL score>= 0.75) (PP3). This variant is absent from gnomAD (PM2_Supporting). |
Rett |
RCV000133060 | SCV000188048 | uncertain significance | Rett syndrome | 2010-12-03 | no assertion criteria provided | curation |