Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000132865 | SCV002769707 | uncertain significance | Rett syndrome | 2022-10-11 | reviewed by expert panel | curation | The p.Ala378Gly variant has been observed in 3 individuals with Rett syndrome (PMID 16473305, 20031356, 11960578) (PS4_moderate). The p.Ala378Gly variant is observed in at least 7 unaffected individuals (internal database - GeneDx; internal database - Invitae) (BS2). The p.Ala378Gly variant in MECP2 is present in 3 female and 1 male individual(s) in gnomAD (0.002%) (not sufficient to meet BS1 criteria). In summary, the p.Ala378Gly variant in MECP2 is classified as a Variant of Uncertain Significance based on the ACMG/AMP criteria (BS2, PS4_moderate). |
Mendelics | RCV000132865 | SCV001142083 | uncertain significance | Rett syndrome | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001245011 | SCV001418271 | likely benign | Severe neonatal-onset encephalopathy with microcephaly | 2023-10-14 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001546726 | SCV001766297 | likely benign | not provided | 2019-09-12 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 16473305, 11960578, 26984561) |
Ambry Genetics | RCV002515927 | SCV003572205 | uncertain significance | Inborn genetic diseases | 2021-09-22 | criteria provided, single submitter | clinical testing | The c.1133C>G (p.A378G) alteration is located in exon 4 (coding exon 3) of the MECP2 gene. This alteration results from a C to G substitution at nucleotide position 1133, causing the alanine (A) at amino acid position 378 to be replaced by a glycine (G). This variant has been detected individuals with classic Rett syndrome and Rett syndrome-like features (Milunsky, 2001; Philippe, 2006; Monnerat, 2010; Zahorakova, 2016). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Revvity Omics, |
RCV001546726 | SCV003810862 | uncertain significance | not provided | 2021-08-12 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003398777 | SCV004105953 | uncertain significance | MECP2-related condition | 2023-06-29 | criteria provided, single submitter | clinical testing | The MECP2 c.1133C>G variant is predicted to result in the amino acid substitution p.Ala378Gly. This variant was reported in three individuals with Rett syndrome or Rett-like features (Milunsky et al. 2001. PubMed ID: 11960578; Philippe et al. 2006. PubMed ID: 16473305; Zahorakova et al. 2016. PubMed ID: 26984561). However, this variant is also reported in 0.0072% of alleles in individuals of Latino descent in gnomAD, including four heterozygotes and one hemizygote (http://gnomad.broadinstitute.org/variant/X-153296146-G-C). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Centre for Population Genomics, |
RCV000132865 | SCV004232286 | uncertain significance | Rett syndrome | 2024-01-10 | 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 a variant of uncertain significance. At least the following criteria are met: The variant is observed in at least 2 individuals with no features of Rett Syndrome (BS2). Has been observed in at least 3 individuals with phenotypes consistent with MECP2-related disease(PS4_Moderate). (PMID: 16473305, 20031356, 11960578) |
Rett |
RCV000132865 | SCV000187845 | uncertain significance | Rett syndrome | 2010-07-13 | no assertion criteria provided | curation |