NM_022455.5(NSD1):c.5990A>G (p.Tyr1997Cys) AND Inborn genetic diseases

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 20, 2016
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:: RCV002354542.9

Allele description [Variation Report for NM_022455.5(NSD1):c.5990A>G (p.Tyr1997Cys)]

NM_022455.5(NSD1):c.5990A>G (p.Tyr1997Cys)

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.5990A>G (p.Tyr1997Cys)

HGVS:

NC_000005.10:g.177282562A>G
NG_009821.1:g.154484A>G
NM_001365684.2:c.5117A>G
NM_001409301.1:c.5990A>G
NM_001409302.1:c.5990A>G
NM_001409303.1:c.5990A>G
NM_001409304.1:c.5570A>G
NM_001409305.1:c.5237A>G
NM_001409306.1:c.5228A>G
NM_001409307.1:c.5228A>G
NM_001409308.1:c.5117A>G
NM_001409309.1:c.5117A>G
NM_022455.5:c.5990A>GMANE SELECT
NM_172349.5:c.5117A>G
NP_001352613.1:p.Tyr1728Cys
NP_001352613.2:p.Tyr1706Cys
NP_001396230.1:p.Tyr1997Cys
NP_001396231.1:p.Tyr1997Cys
NP_001396232.1:p.Tyr1997Cys
NP_001396233.1:p.Tyr1857Cys
NP_001396234.1:p.Tyr1746Cys
NP_001396235.1:p.Tyr1743Cys
NP_001396236.1:p.Tyr1743Cys
NP_001396237.1:p.Tyr1706Cys
NP_001396238.1:p.Tyr1706Cys
NP_071900.2:p.Tyr1997Cys
NP_071900.2:p.Tyr1997Cys
NP_758859.1:p.Tyr1728Cys
NP_758859.2:p.Tyr1706Cys
LRG_512t1:c.5990A>G
LRG_512:g.154484A>G
LRG_512p1:p.Tyr1997Cys
NC_000005.9:g.176709563A>G
NM_001365684.1:c.5183A>G
NM_022455.4:c.5990A>G
NM_172349.3:c.5183A>G
Q96L73:p.Tyr1997Cys

Protein change:

Y1706C

Links:

UniProtKB: Q96L73#VAR_015788; dbSNP: rs797045825

NCBI 1000 Genomes Browser:

rs797045825

Molecular consequence:

NM_001365684.2:c.5117A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001409301.1:c.5990A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001409302.1:c.5990A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001409303.1:c.5990A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001409304.1:c.5570A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001409305.1:c.5237A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001409306.1:c.5228A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001409307.1:c.5228A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001409308.1:c.5117A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001409309.1:c.5117A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_022455.5:c.5990A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172349.5:c.5117A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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mitochondrial basic amino acids transporter isoform X1 [Leucoraja erinaceus]
mitochondrial basic amino acids transporter isoform X1 [Leucoraja erinaceus]
gi|2497505532|ref|XP_055497133.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002655725	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Sep 20, 2016)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 12807965, 15942875, 24412544, 26690673 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002655725

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Sep 20, 2016)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

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

Spectrum of NSD1 mutations in Sotos and Weaver syndromes.

Rio M, Clech L, Amiel J, Faivre L, Lyonnet S, Le Merrer M, Odent S, Lacombe D, Edery P, Brauner R, Raoul O, Gosset P, Prieur M, Vekemans M, Munnich A, Colleaux L, Cormier-Daire V.

J Med Genet. 2003 Jun;40(6):436-40.

PubMed [citation]

PMID:: 12807965
PMCID:: PMC1735492

Genotype-phenotype associations in Sotos syndrome: an analysis of 266 individuals with NSD1 aberrations.

Tatton-Brown K, Douglas J, Coleman K, Baujat G, Cole TR, Das S, Horn D, Hughes HE, Temple IK, Faravelli F, Waggoner D, Turkmen S, Cormier-Daire V, Irrthum A, Rahman N; Childhood Overgrowth Collaboration..

Am J Hum Genet. 2005 Aug;77(2):193-204. Epub 2005 Jun 7.

PubMed [citation]

PMID:: 15942875
PMCID:: PMC1224542

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV002655725.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

The p.Y1997C pathogenic mutation (also known as c.5990A>G), located in coding exon 18 of the NSD1 gene, results from an A to G substitution at nucleotide position 5990. The tyrosine at codon 1997 is replaced by cysteine, an amino acid with highly dissimilar properties. This mutation was first reported to be de novo in a patient with childhood overgrowth, dysmorphic facial features, and advanced bone age (Rio M et al. J. Med. Genet., 2003 Jun;40:436-40). It has subsequently been reported in multiple individuals with Sotos syndrome phenotypes (Tatton-Brown K et al. Am. J. Hum. Genet., 2005 Aug;77:193-204; Choufani S et al. Nat Commun, 2015 Dec;6:10207). Additionally, in vitro functional studies showed the p.Y1997C mutation results in reduced or abolished enzyme methylation activity (Kudithipudi S et al. Chem. Biol., 2014 Feb;21:226-37). Based on the supporting evidence, p.Y1997C is interpreted as a disease-causing mutation.

#	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: Oct 13, 2024

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