NM_022455.5(NSD1):c.5143G>T (p.Glu1715Ter) AND Sotos syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 16, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003232701.8

Allele description

NM_022455.5(NSD1):c.5143G>T (p.Glu1715Ter)

Gene:

NSD1:nuclear receptor binding SET domain protein 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q35.3

Genomic location:

Preferred name:

NM_022455.5(NSD1):c.5143G>T (p.Glu1715Ter)

HGVS:

NC_000005.10:g.177260165G>T
NG_009821.1:g.132087G>T
NM_001365684.2:c.4270G>T
NM_001409301.1:c.5143G>T
NM_001409302.1:c.5143G>T
NM_001409303.1:c.5143G>T
NM_001409304.1:c.4723G>T
NM_001409305.1:c.4390G>T
NM_001409306.1:c.4381G>T
NM_001409307.1:c.4381G>T
NM_001409308.1:c.4270G>T
NM_001409309.1:c.4270G>T
NM_022455.5:c.5143G>TMANE SELECT
NM_172349.5:c.4270G>T
NP_001352613.1:p.Glu1446Ter
NP_001352613.2:p.Glu1424Ter
NP_001396230.1:p.Glu1715Ter
NP_001396231.1:p.Glu1715Ter
NP_001396232.1:p.Glu1715Ter
NP_001396233.1:p.Glu1575Ter
NP_001396234.1:p.Glu1464Ter
NP_001396235.1:p.Glu1461Ter
NP_001396236.1:p.Glu1461Ter
NP_001396237.1:p.Glu1424Ter
NP_001396238.1:p.Glu1424Ter
NP_071900.2:p.Glu1715Ter
NP_071900.2:p.Glu1715Ter
NP_758859.1:p.Glu1446Ter
NP_758859.2:p.Glu1424Ter
LRG_512t1:c.5143G>T
LRG_512:g.132087G>T
LRG_512p1:p.Glu1715Ter
NC_000005.9:g.176687166G>T
NM_001365684.1:c.4336G>T
NM_022455.4:c.5143G>T
NM_172349.3:c.4336G>T

Protein change:

E1424*

Molecular consequence:

NM_001365684.2:c.4270G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001409301.1:c.5143G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001409302.1:c.5143G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001409303.1:c.5143G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001409304.1:c.4723G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001409305.1:c.4390G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001409306.1:c.4381G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001409307.1:c.4381G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001409308.1:c.4270G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001409309.1:c.4270G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_022455.5:c.5143G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_172349.5:c.4270G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Sotos syndrome (SOTOS)
Synonyms:: Sotos' syndrome; Cerebral gigantism; Distinctive facial appearance, overgrowth in childhood, and learning disabilities or delayed development; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0019349; MedGen: C0175695; Orphanet: 821; OMIM: 117550

Recent activity

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Photocorynus spiniceps voucher G002 PolB (polb) mRNA, complete cds
Photocorynus spiniceps voucher G002 PolB (polb) mRNA, complete cds
gi|2548500718|gb|OR295606.1|

Nucleotide
Trichomycterus hasemani voucher UFRJ<museum>:9712 16S ribosomal RNA gene, partia...
Trichomycterus hasemani voucher UFRJ<museum>:9712 16S ribosomal RNA gene, partial sequence; mitochondrial
gi|1273122385|gb|MF434087.1|

Nucleotide
CBST3145.rev NICHD_XGC_tropThy1 Xenopus tropicalis cDNA clone IMAGE:8924253 3', ...
CBST3145.rev NICHD_XGC_tropThy1 Xenopus tropicalis cDNA clone IMAGE:8924253 3', mRNA sequence
gi|126550084|gnl|dbEST|45063958|gb| 599.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003233118	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 16, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 12464997, 14571271, 15942875, 16247291, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003233118

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 16, 2022)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

NSD1 mutations are the major cause of Sotos syndrome and occur in some cases of Weaver syndrome but are rare in other overgrowth phenotypes.

Douglas J, Hanks S, Temple IK, Davies S, Murray A, Upadhyaya M, Tomkins S, Hughes HE, Cole TR, Rahman N.

Am J Hum Genet. 2003 Jan;72(1):132-43. Epub 2002 Dec 2.

PubMed [citation]

PMID:: 12464997
PMCID:: PMC378618

Mutations in NSD1 are responsible for Sotos syndrome, but are not a frequent finding in other overgrowth phenotypes.

Türkmen S, Gillessen-Kaesbach G, Meinecke P, Albrecht B, Neumann LM, Hesse V, Palanduz S, Balg S, Majewski F, Fuchs S, Zschieschang P, Greiwe M, Mennicke K, Kreuz FR, Dehmel HJ, Rodeck B, Kunze J, Tinschert S, Mundlos S, Horn D.

Eur J Hum Genet. 2003 Nov;11(11):858-65.

PubMed [citation]

PMID:: 14571271

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV003233118.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Glu1715*) 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 (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NSD1-related conditions. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 16, 2024

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