Submissions for variant NM_001271.4(CHD2):c.3938G>A (p.Arg1313Gln)

dbSNP: rs1131692012

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000494676	SCV000583362	uncertain significance	not provided	2017-05-01	criteria provided, single submitter	clinical testing	The R1313Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. However, a different missense variant at the same position (R1313G) has been reported previously in an individual with photosensitive epilepsy (Galizia et al., 2015). The R1313Q variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R1313Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001856984	SCV002238042	pathogenic	Developmental and epileptic encephalopathy 94	2022-08-16	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg1313 amino acid residue in CHD2. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 430536). This missense change has been observed in individual(s) with clinical features of CHD2-related conditions (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1313 of the CHD2 protein (p.Arg1313Gln).