NM_000448.3(RAG1):c.2029C>G (p.Pro677Ala) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 14, 2021
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:: RCV001909108.5

Allele description [Variation Report for NM_000448.3(RAG1):c.2029C>G (p.Pro677Ala)]

NM_000448.3(RAG1):c.2029C>G (p.Pro677Ala)

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.2029C>G (p.Pro677Ala)

HGVS:

NC_000011.10:g.36575333C>G
NG_007528.1:g.12321C>G
NM_000448.3:c.2029C>GMANE SELECT
NM_001377277.1:c.2029C>G
NM_001377278.1:c.2029C>G
NM_001377279.1:c.2029C>G
NM_001377280.1:c.2029C>G
NP_000439.2:p.Pro677Ala
NP_001364206.1:p.Pro677Ala
NP_001364207.1:p.Pro677Ala
NP_001364208.1:p.Pro677Ala
NP_001364209.1:p.Pro677Ala
LRG_98t1:c.2029C>G
LRG_98:g.12321C>G
NC_000011.9:g.36596883C>G
NM_000448.2:c.2029C>G

Protein change:

P677A

Links:

dbSNP: rs773165685

NCBI 1000 Genomes Browser:

rs773165685

Molecular consequence:

NM_000448.3:c.2029C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001377277.1:c.2029C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001377278.1:c.2029C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001377279.1:c.2029C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001377280.1:c.2029C>G - 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

Clear Turn Off Turn On

Chain K, Exosome complex exonuclease RRP44
Chain K, Exosome complex exonuclease RRP44
gi|1407938519|pdb|6D6Q|K

Protein

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002173800	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 14, 2021)	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

SCV002173800

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 14, 2021)

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, SCV002173800.2

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

Description

This sequence change replaces proline with alanine at codon 677 of the RAG1 protein (p.Pro677Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with RAG1-related conditions. 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 expected to disrupt RAG1 protein function. 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.

#	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

ClinVar

Relating variation to medicine