Submissions for variant NM_004415.4(DSP):c.1783C>T (p.Gln595Ter)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Génétique des Maladies du Développement, Hospices Civils de Lyon	RCV001255417	SCV001431817	pathogenic	Global developmental delay	2019-11-01	criteria provided, single submitter	clinical testing
Departamento de Patología, Instituto de Genética, Universidad Nacional de Colombia	RCV001568353	SCV001792210	pathogenic	Arrhythmogenic right ventricular dysplasia 8	2021-07-16	criteria provided, single submitter	clinical testing	The p.Q595 pathogenic variant, located in coding exon 14 of the DSP gene, results from a C to T substitution at nucleotide position 595 which creates a stop codon. Null variants in the DSP gene cause loss of function which is a known mechanism of arrhythmogenic cardiomyopathy. This variant is not found in gnomAD exomes or genomes. Pathogenic computational verdict based on 5 pathogenic predictions from BayesDel_addAF, DANN, EIGEN, FATHMM-MKL and MutationTaster vs no benign predictions. In summary, this variant meets criteria to be classified as pathogenic. PVS1, PM2, PP3, PP5
GeneDx	RCV003156331	SCV003845627	likely pathogenic	not provided	2023-03-27	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease