ClinVar Miner

Submissions for variant NM_001110792.2(MECP2):c.1150C>T (p.His384Tyr) (rs375477214)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,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 uncertain significance Severe neonatal-onset encephalopathy with microcephaly 2019-10-03 criteria provided, single submitter clinical testing This sequence change replaces histidine with tyrosine at codon 372 of the MECP2 protein (p.His372Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MECP2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0". The tyrosine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.