Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003448359 | SCV004175918 | likely benign | Rett syndrome | 2023-10-13 | reviewed by expert panel | curation | The p.His372Tyr variant in MECP2 (NM_004992.3) is present in 2 female individuals in gnomAD (0.001%) (not sufficient to meet BS1 criteria). The p.His372Tyr variant is observed in at least 3 unaffected individuals (internal database - Invitae) (BS2). In the absence of conflicting evidence, this is sufficient evidence to classify as likely benign based on the specifications defined by the ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel. In summary, the p.His372Tyr variant in MECP2 is classified as Likely Benign based on the ACMG/AMP criteria (BS2). |
ARUP Laboratories, |
RCV001000154 | SCV001156639 | uncertain significance | not specified | 2018-08-06 | criteria provided, single submitter | clinical testing | The MECP2 c.1114C>T; p.His372Tyr variant (rs375477214), to our knowledge, is not reported in the medical literature but is reported once in the RettBASE database (see link). This variant is found in the general population with an overall allele frequency of 0.001% (2/174376 alleles) in the Genome Aggregation Database. The histidine at codon 372 is moderately conserved, but computational analyses (SIFT, PolyPhen-2) predict this variant to be tolerated. Given the lack of clinical and functional data, the significance of the p.His372Tyr variant is uncertain at this time. REFERENCES RettBASE Variation Database link: http://mecp2.chw.edu.au/cgi-bin/mecp2/views/basic.cgi?form=basic |
Invitae | RCV001242465 | SCV001415557 | benign | Severe neonatal-onset encephalopathy with microcephaly | 2023-10-16 | criteria provided, single submitter | clinical testing | |
Centre for Population Genomics, |
RCV003448359 | SCV004232222 | likely benign | 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: The variant is observed in at least 2 individuals with no features of Rett Syndrome (BS2). |