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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