Submissions for variant NM_001195553.2(DCX):c.667G>A (p.Gly223Arg)

dbSNP: rs587783577

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000145880	SCV000193017	pathogenic	Ectopic tissue	2014-07-07	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000996004	SCV001150428	uncertain significance	not provided	2019-05-01	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV003144138	SCV003834297	uncertain significance	Lissencephaly type 1 due to doublecortin gene mutation	2020-03-17	criteria provided, single submitter	clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000996004	SCV004026036	pathogenic	not provided	2022-05-10	criteria provided, single submitter	clinical testing	PS1, PS2, PM1, PM2_SUP
Labcorp Genetics (formerly Invitae), Labcorp	RCV000996004	SCV004641543	pathogenic	not provided	2023-12-05	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 223 of the DCX protein (p.Gly223Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with lissencephaly and subcortical band heterotopia (PMID: 31069529, 32570172, 34145886). In at least one individual the variant was observed to be de novo. This variant is also known as c.910G>A, p.Gly304Arg . ClinVar contains an entry for this variant (Variation ID: 158496). 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 expected to disrupt DCX protein function with a positive predictive value of 80%. This variant disrupts the p.Gly223 amino acid residue in DCX. Other variant(s) that disrupt this residue have been observed in individuals with DCX-related conditions (PMID: 9618162, 11175293), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV003144138	SCV005418090	uncertain significance	Lissencephaly type 1 due to doublecortin gene mutation		criteria provided, single submitter	clinical testing	PM2_Supporting+PP4+PP3+PS4_Supporting