ClinVar Miner

Submissions for variant NM_001110792.2(MECP2):c.1469G>A (p.Arg490Gln) (rs145790362)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000767162 SCV000191002 uncertain significance not provided 2016-07-01 criteria provided, single submitter clinical testing The Arg478Gln missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The amino acid substitution is non-conservative, as a positively charged Arginine residue is replaced by an uncharged Glutamine residue, and it alters a highly conserved position in the C-terminal domain of the MECP2 protein. However, missense substitutions at nearby codons are classified as benign variants, suggesting that this region of the protein is tolerant of missense changes. Several in silico algorithms predict that Arg478Gln is likely benign, although another model suggests it may be damaging to protein structure/function. Therefore, based on the available information it is currently unclear whether Arg478Gln is a disease-causing mutation or a rare benign variant. The variant is found in CHILD-EPI panel(s).
Fulgent Genetics,Fulgent Genetics RCV000766080 SCV000897555 uncertain significance Severe neonatal-onset encephalopathy with microcephaly; Syndromic X-linked intellectual disability Lubs type; Mental retardation, X-linked, syndromic 13; Rett syndrome; Autism, susceptibility to, X-linked 3 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV001048888 SCV001212916 uncertain significance Severe neonatal-onset encephalopathy with microcephaly 2019-12-11 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 478 of the MECP2 protein (p.Arg478Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. 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. ClinVar contains an entry for this variant (Variation ID: 156636). 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.
RettBASE RCV000170088 SCV000222404 benign not specified 2013-12-05 no assertion criteria provided curation

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