NM_000448.3(RAG1):c.3053C>T (p.Thr1018Ile) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 1, 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:: RCV001963889.4

Allele description [Variation Report for NM_000448.3(RAG1):c.3053C>T (p.Thr1018Ile)]

NM_000448.3(RAG1):c.3053C>T (p.Thr1018Ile)

Gene:

RAG1:recombination activating 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p12

Genomic location:

Preferred name:

NM_000448.3(RAG1):c.3053C>T (p.Thr1018Ile)

HGVS:

NC_000011.10:g.36576357C>T
NG_007528.1:g.13345C>T
NM_000448.3:c.3053C>TMANE SELECT
NM_001377277.1:c.3053C>T
NM_001377278.1:c.3053C>T
NM_001377279.1:c.3053C>T
NM_001377280.1:c.3053C>T
NP_000439.2:p.Thr1018Ile
NP_001364206.1:p.Thr1018Ile
NP_001364207.1:p.Thr1018Ile
NP_001364208.1:p.Thr1018Ile
NP_001364209.1:p.Thr1018Ile
LRG_98:g.13345C>T
NC_000011.9:g.36597907C>T

Protein change:

T1018I

Links:

dbSNP: rs748782315

NCBI 1000 Genomes Browser:

rs748782315

Molecular consequence:

NM_000448.3:c.3053C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001377277.1:c.3053C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001377278.1:c.3053C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001377279.1:c.3053C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001377280.1:c.3053C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Combined immunodeficiency with skin granulomas
Synonyms:: Combined cellular and humoral immune defects with granulomas
Identifiers:: MONDO: MONDO:0009306; MedGen: C2673536; OMIM: 233650

Name:: Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive
Synonyms:: SCID, T CELL-NEGATIVE, B CELL-NEGATIVE, NK CELL-POSITIVE; Severe immunodeficiency, autosomal recessive, T-cell negative, B-cell negative, NK cell-positive; SCID, AR, T-cell negative, B-cell negative, NK cell-positive; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011086; MedGen: C1832322; Orphanet: 331206; OMIM: 601457

Recent activity

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Mus musculus ectonucleotide pyrophosphatase/phosphodiesterase 4 (Enpp4), mRNA
Mus musculus ectonucleotide pyrophosphatase/phosphodiesterase 4 (Enpp4), mRNA
gi|39841030|ref|NM_199016.1|

Nucleotide
ectoderm-neural cortex protein 1 isoform 1 [Homo sapiens]
ectoderm-neural cortex protein 1 isoform 1 [Homo sapiens]
gi|375268724|ref|NP_001243504.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002249840	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 1, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002249840

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 1, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002249840.3

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RAG1 protein function. ClinVar contains an entry for this variant (Variation ID: 1466134). This variant has not been reported in the literature in individuals affected with RAG1-related conditions. This variant is present in population databases (rs748782315, gnomAD 0.01%). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1018 of the RAG1 protein (p.Thr1018Ile).

#	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 29, 2024

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Relating variation to medicine