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NM_000448.3(RAG1):c.3074dup (p.Leu1025fs) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 14, 2023
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:
RCV001956054.6

Allele description [Variation Report for NM_000448.3(RAG1):c.3074dup (p.Leu1025fs)]

NM_000448.3(RAG1):c.3074dup (p.Leu1025fs)

Gene:
RAG1:recombination activating 1 [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
11p12
Genomic location:
Preferred name:
NM_000448.3(RAG1):c.3074dup (p.Leu1025fs)
HGVS:
  • NC_000011.10:g.36576378dup
  • NG_007528.1:g.13366dup
  • NM_000448.3:c.3074dupMANE SELECT
  • NM_001377277.1:c.3074dup
  • NM_001377278.1:c.3074dup
  • NM_001377279.1:c.3074dup
  • NM_001377280.1:c.3074dup
  • NP_000439.2:p.Leu1025fs
  • NP_001364206.1:p.Leu1025fs
  • NP_001364207.1:p.Leu1025fs
  • NP_001364208.1:p.Leu1025fs
  • NP_001364209.1:p.Leu1025fs
  • LRG_98:g.13366dup
  • NC_000011.9:g.36597926_36597927insT
  • NC_000011.9:g.36597928dup
Protein change:
L1025fs
Links:
dbSNP: rs1564990390
NCBI 1000 Genomes Browser:
rs1564990390
Molecular consequence:
  • NM_000448.3:c.3074dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001377277.1:c.3074dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001377278.1:c.3074dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001377279.1:c.3074dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001377280.1:c.3074dup - frameshift variant - [Sequence Ontology: SO:0001589]

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002240701Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(May 14, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Clinical, immunologic, and genetic characteristics of RAG mutations in 15 Chinese patients with SCID and Omenn syndrome.

Bai X, Liu J, Zhang Z, Liu C, Zhang Y, Tang W, Dai R, Wu J, Tang X, Zhang Y, Ding Y, Jiang L, Zhao X.

Immunol Res. 2016 Apr;64(2):497-507. doi: 10.1007/s12026-015-8723-4.

PubMed [citation]
PMID:
26476733

Family History of Early Infant Death Correlates with Earlier Age at Diagnosis But Not Shorter Time to Diagnosis for Severe Combined Immunodeficiency.

Luk ADW, Lee PP, Mao H, Chan KW, Chen XY, Chen TX, He JX, Kechout N, Suri D, Tao YB, Xu YB, Jiang LP, Liew WK, Jirapongsananuruk O, Daengsuwan T, Gupta A, Singh S, Rawat A, Abdul Latiff AH, Lee ACW, Shek LP, Nguyen TVA, et al.

Front Immunol. 2017;8:808. doi: 10.3389/fimmu.2017.00808.

PubMed [citation]
PMID:
28747913
PMCID:
PMC5506088
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002240701.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1457784). This variant is also known as c.3198_3199insT (p.L1025FfsX39). This frameshift has been observed in individuals with severe combined immunodeficiency or Omenn syndrome (PMID: 26476733, 28747913). This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the RAG1 gene (p.Leu1025Phefs*40). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 19 amino acid(s) of the RAG1 protein and extend the protein by 20 additional amino acid residues.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024