Submissions for variant NM_003737.4(DCHS1):c.704G>A (p.Arg235Gln)

gnomAD frequency: 0.00077  dbSNP: rs143767864

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000519012	SCV000620335	uncertain significance	not provided	2024-04-20	criteria provided, single submitter	clinical testing	Reported in an individual tested as part of a sudden infant death syndrome cohort in published literature; additional information was not provided (PMID: 28074886); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 28074886)
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000519012	SCV001472343	uncertain significance	not provided	2019-10-30	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001336075	SCV001529369	uncertain significance	Van Maldergem syndrome 1	2018-04-02	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Labcorp Genetics (formerly Invitae), Labcorp	RCV000519012	SCV002343921	likely benign	not provided	2025-01-28	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002525209	SCV003530289	likely benign	Inborn genetic diseases	2022-02-04	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.
Neuberg Centre For Genomic Medicine, NCGM	RCV001336075	SCV004048542	uncertain significance	Van Maldergem syndrome 1		criteria provided, single submitter	clinical testing	The missense variant in c.704G>A (p.Arg235Gln) in DCHS1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Arg235Gln variant is reported with the allele frequency of 0.09151% in gnomAD database and is novel (not in any individuals) in 1000 Genomes. The amino acid Arg at position 235 is changed to a Gln changing protein sequence and it might alter its composition and physico-chemical properties. This variant has been reported to the ClinVar database as Uncertain significance. The variant is predicted to be damaging by PolyPhen2 and the residue is conserved across species. The amino acid change p.Arg235Gln in DCHS1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates For these reasons, this variant has been classified as Uncertain Significance. In the absence of another reportable variant the molecular diagnosis is not confirmed.
CeGaT Center for Human Genetics Tuebingen	RCV000519012	SCV004135916	likely benign	not provided	2024-09-01	criteria provided, single submitter	clinical testing	DCHS1: BP4