Submissions for variant NM_001376.5(DYNC1H1):c.874C>T (p.Arg292Trp)

dbSNP: rs2047850664

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Cavalleri Lab, Royal College of Surgeons in Ireland	RCV001030994	SCV001027104	pathogenic	Intellectual disability, autosomal dominant 13	2019-12-11	criteria provided, single submitter	research	DYNCH1H1 variant is assumed to be pathogenic and probably causative for the clinical features of the patient. ACMG evidences- PS2, PM2, PP2, PP3.
Invitae	RCV001858605	SCV002295637	pathogenic	Charcot-Marie-Tooth disease axonal type 2O	2023-10-13	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 292 of the DYNC1H1 protein (p.Arg292Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of DYNC1H1-related intellectual disability syndrome with cortical brain malformations (PMID: 32238909, 35099838). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 800542). 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 DYNC1H1 protein function. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV002372705	SCV002685081	uncertain significance	Inborn genetic diseases	2018-06-22	criteria provided, single submitter	clinical testing	The p.R292W variant (also known as c.874C>T), located in coding exon 5 of the DYNC1H1 gene, results from a C to T substitution at nucleotide position 874. The arginine at codon 292 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Institute of Human Genetics, University of Leipzig Medical Center	RCV001030994	SCV003921031	likely pathogenic	Intellectual disability, autosomal dominant 13	2023-03-29	criteria provided, single submitter	clinical testing	Criteria applied: PS2_MOD,PS4_MOD,PM2_SUP,PP2
Tongji Hospital, Huazhong University of Science and Technology	RCV001030994	SCV001244188	pathogenic	Intellectual disability, autosomal dominant 13		no assertion criteria provided	clinical testing