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NM_000448.3(RAG1):c.2333G>A (p.Arg778Gln) AND not provided

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Mar 14, 2017
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:
RCV000479659.2

Allele description [Variation Report for NM_000448.3(RAG1):c.2333G>A (p.Arg778Gln)]

NM_000448.3(RAG1):c.2333G>A (p.Arg778Gln)

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.2333G>A (p.Arg778Gln)
HGVS:
  • NC_000011.10:g.36575637G>A
  • NG_007528.1:g.12625G>A
  • NM_000448.3:c.2333G>AMANE SELECT
  • NM_001377277.1:c.2333G>A
  • NM_001377278.1:c.2333G>A
  • NM_001377279.1:c.2333G>A
  • NM_001377280.1:c.2333G>A
  • NP_000439.1:p.Arg778Gln
  • NP_000439.2:p.Arg778Gln
  • NP_001364206.1:p.Arg778Gln
  • NP_001364207.1:p.Arg778Gln
  • NP_001364208.1:p.Arg778Gln
  • NP_001364209.1:p.Arg778Gln
  • LRG_98t1:c.2333G>A
  • LRG_98:g.12625G>A
  • LRG_98p1:p.Arg778Gln
  • NC_000011.9:g.36597187G>A
  • NM_000448.2:c.2333G>A
  • P15918:p.Arg778Gln
Protein change:
R778Q; ARG778GLN
Links:
UniProtKB: P15918#VAR_045958; OMIM: 179615.0020; dbSNP: rs121918569
NCBI 1000 Genomes Browser:
rs121918569
Molecular consequence:
  • NM_000448.3:c.2333G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001377277.1:c.2333G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001377278.1:c.2333G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001377279.1:c.2333G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001377280.1:c.2333G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000568504GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Pathogenic
(Mar 14, 2017) 		germlineclinical testing

Citation Link

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Summary from all submissions

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

Details of each submission

From GeneDx, SCV000568504.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The R778Q variant has been published previously in association with RAG1-associated disorders (Schuetz et al., 2008; Nijman et al., 2014; Kumánovics et al., 2017). The variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). R778Q is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species; in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. However, functional studies have shown R778Q significantly reduces V(D)J recombination activity in comparison to wild-type (Schuetz et al., 2008; Lee et al., 2014). Additionally, missense variants in the same codon (R778G/W) and in a nearby residue (R776W/Q) have been reported in the Human Gene Mutation Database in association with RAG1-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. In summary, we consider this variant to be pathogenic.

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

Last Updated: Apr 7, 2025