ClinVar Miner

Submissions for variant NM_001110792.2(MECP2):c.1169C>G (p.Ala390Gly)

dbSNP: rs201314910
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel RCV000132865 SCV002769707 likely benign Rett syndrome 2024-10-30 reviewed by expert panel curation The p.Ala378Gly variant in MECP2 (NM_004992.4) is observed in at least 7 unaffected individuals (internal database - GeneDx; internal database - Invitae) (BS2). The p.Ala378Gly variant is found in a patient with an alternate molecular basis of disease (internal database - Invitae) (BP5). The highest population minor allele frequency of the p.Ala378Gly variant in MECP2 in gnomAD v4.1 is 0.00006606 in Admixed American population (not sufficient to meet BS1 criteria). In summary, the p.Ala378Gly variant in MECP2 is classified as Likely Benign based on the ACMG/AMP criteria (BS2, BP5).
Mendelics RCV000132865 SCV001142083 uncertain significance Rett syndrome 2019-05-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001245011 SCV001418271 likely benign Severe neonatal-onset encephalopathy with microcephaly 2024-10-24 criteria provided, single submitter clinical testing
GeneDx 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, Revvity RCV001546726 SCV003810862 uncertain significance not provided 2021-08-12 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004528866 SCV004105953 uncertain significance MECP2-related disorder 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, CPG 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)
RettBASE RCV000132865 SCV000187845 uncertain significance Rett syndrome 2010-07-13 no assertion criteria provided curation

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