Submissions for variant NM_001271.4(CHD2):c.4814A>C (p.Lys1605Thr)

gnomAD frequency: 0.00006  dbSNP: rs780701076

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000480398	SCV000571616	likely benign	not provided	2020-02-12	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002318580	SCV000850403	likely benign	Inborn genetic diseases	2017-01-25	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001244394	SCV001417614	uncertain significance	Developmental and epileptic encephalopathy 94	2024-01-30	criteria provided, single submitter	clinical testing	This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 1605 of the CHD2 protein (p.Lys1605Thr). This variant is present in population databases (rs780701076, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CHD2-related conditions. ClinVar contains an entry for this variant (Variation ID: 422208). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CHD2 protein function with a negative predictive value of 95%. 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001244394	SCV003799573	uncertain significance	Developmental and epileptic encephalopathy 94	2022-04-08	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000480398	SCV004130952	likely benign	not provided	2022-06-01	criteria provided, single submitter	clinical testing	CHD2: BS2