Submissions for variant NM_022455.5(NSD1):c.1492C>T (p.Arg498Ter)

dbSNP: rs1581315609

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003232110	SCV001586068	pathogenic	Sotos syndrome	2021-08-27	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg498*) in the NSD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NSD1 are known to be pathogenic (PMID: 12464997, 14571271, 15942875, 16247291). This variant is not present in population databases (ExAC no frequency). This premature translational stop signal has been observed in individual(s) with Sotos-like syndrome (PMID: 12464997). For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV001796231	SCV002032773	pathogenic	not provided	2022-12-06	criteria provided, single submitter	clinical testing	Identified in patients with Sotos syndrome or Sotos-like phenotype (Douglas et al., 2003; Turkmen at al., 2003; Tatton-Brown et al., 2005; Saugier-Veber et al., 2007); 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; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 12464997, 14571271, 15942875, 30202406, 17565729, 34386909)
Genome-Nilou Lab	RCV003232110	SCV002054912	pathogenic	Sotos syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Department of Rehabilitation Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea	RCV003232110	SCV004023325	pathogenic	Sotos syndrome		no assertion criteria provided	clinical testing