Submissions for variant NM_022455.5(NSD1):c.1831C>T (p.Arg611Ter)

dbSNP: rs587784077

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV003231177	SCV000194096	pathogenic	Sotos syndrome	2013-02-08	criteria provided, single submitter	clinical testing
GeneDx	RCV000294223	SCV000329435	pathogenic	not provided	2023-03-30	criteria provided, single submitter	clinical testing	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, 31785789, 29276005, 28475857, 15942875)
Johns Hopkins Genomics, Johns Hopkins University	RCV003231177	SCV000886722	pathogenic	Sotos syndrome	2019-01-17	criteria provided, single submitter	clinical testing	This NSD1 variant has been previous been reported in individuals with a clinical presentation consistent with Sotos syndrome. Two submitters in ClinVar classify this variant as pathogenic. Additionally this variant is absent from large population datasets. This nonsense variant in exon 5 of 23 likely results in nonsense-mediated decay and lack of protein production. This variant is considered pathogenic.
Genome-Nilou Lab	RCV003231177	SCV002054914	pathogenic	Sotos syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV003231177	SCV002247256	pathogenic	Sotos syndrome	2021-09-01	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg611*) 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 clinical features of Sotos syndrome (PMID: 28475857, 29276005). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 159273). For these reasons, this variant has been classified as Pathogenic.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV003231177	SCV002512628	pathogenic	Sotos syndrome	2021-08-15	criteria provided, single submitter	clinical testing	ACMG classification criteria: PVS1 very strong, PS4 strong, PM2 moderate, PM6 strong
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille	RCV003231177	SCV001427830	pathogenic	Sotos syndrome	2019-01-01	no assertion criteria provided	clinical testing