Submissions for variant NM_022455.5(NSD1):c.3422del (p.Met1141fs)

dbSNP: rs1554190247

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000527387	SCV000623202	pathogenic	Beckwith-Wiedemann syndrome	2017-03-26	criteria provided, single submitter	clinical testing	This sequence change deletes 1 nucleotide from exon 5 of the NSD1 mRNA (c.3422delT), causing a frameshift at codon 1141. This creates a premature translational stop signal (p.Met1141Argfs*11) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in NSD1 are known to be pathogenic (PMID: 12807965, 15942875, 17565729). For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003231635	SCV001579183	pathogenic	Sotos syndrome	2020-02-14	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Met1141Argfs*11) in the NSD1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NSD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 454049). Loss-of-function variants in NSD1 are known to be pathogenic (PMID: 12464997, 14571271, 15942875, 16247291). For these reasons, this variant has been classified as Pathogenic.