Submissions for variant NM_001271.4(CHD2):c.5202A>C (p.Gln1734His)

dbSNP: rs1009699195

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000486684	SCV000569196	uncertain significance	not provided	2016-02-04	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the CHD2 gene. The Q1734H variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The Q1734H variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Additionally, this substitution occurs at a position that is conserved in mammals. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, 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	RCV000709848	SCV001544818	uncertain significance	Developmental and epileptic encephalopathy 94	2020-03-17	criteria provided, single submitter	clinical testing	This variant is not present in population databases (ExAC no frequency). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CHD2-related conditions. ClinVar contains an entry for this variant (Variation ID: 420381). This sequence change replaces glutamine with histidine at codon 1734 of the CHD2 protein (p.Gln1734His). The glutamine residue is weakly conserved and there is a small physicochemical difference between glutamine and histidine.
Revvity Omics, Revvity	RCV000709848	SCV003833275	uncertain significance	Developmental and epileptic encephalopathy 94	2021-12-31	criteria provided, single submitter	clinical testing
GenomeConnect, ClinGen	RCV000709848	SCV000840180	not provided	Developmental and epileptic encephalopathy 94		no assertion provided	phenotyping only	GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.