NM_005633.4(SOS1):c.1654A>T (p.Arg552Trp) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Mar 9, 2018
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000414145.3

Allele description [Variation Report for NM_005633.4(SOS1):c.1654A>T (p.Arg552Trp)]

NM_005633.4(SOS1):c.1654A>T (p.Arg552Trp)

Gene:

SOS1:SOS Ras/Rac guanine nucleotide exchange factor 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p22.1

Genomic location:

Preferred name:

NM_005633.4(SOS1):c.1654A>T (p.Arg552Trp)

Other names:

NM_005633.3(SOS1):c.1654A>T

HGVS:

NC_000002.12:g.39022774T>A
NG_007530.1:g.102690A>T
NM_001382394.1:c.1633A>T
NM_001382395.1:c.1654A>T
NM_005633.4:c.1654A>TMANE SELECT
NP_001369323.1:p.Arg545Trp
NP_001369324.1:p.Arg552Trp
NP_005624.2:p.Arg552Trp
NP_005624.2:p.Arg552Trp
LRG_754t1:c.1654A>T
LRG_754:g.102690A>T
LRG_754p1:p.Arg552Trp
NC_000002.11:g.39249915T>A
NM_005633.3:c.1654A>T

Protein change:

R545W

Links:

dbSNP: rs137852814

NCBI 1000 Genomes Browser:

rs137852814

Molecular consequence:

NM_001382394.1:c.1633A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382395.1:c.1654A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_005633.4:c.1654A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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LOC108342829 [Vigna angularis]
LOC108342829 [Vigna angularis]
Gene ID:108342829

Gene
SC5D [Apteryx rowi]
SC5D [Apteryx rowi]
Gene ID:112968933

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000491038	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Aug 3, 2015)	germline	clinical testing	Citation Link,
SCV000927585	Blueprint Genetics	criteria provided, single submitter (Blueprint Genetics Variant Classification Scheme)	Likely pathogenic (Mar 9, 2018)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000491038

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Aug 3, 2015)

germline

clinical testing

Citation Link,

SCV000927585

Blueprint Genetics

criteria provided, single submitter

(Blueprint Genetics Variant Classification Scheme)

Likely pathogenic
(Mar 9, 2018)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000491038.2

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

Description

The R552W in the SOS1 gene has been reported in one family in association with pulmonary stenosis and Noonan syndrome (Ezquieta et al., 2012). Additionally, the R552W variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. R552W results in a non-conservative amino acid substitution at a position that is conserved across species. Several other missense variants have been reported in the same residue (R552G, R552T, G552K, R552M, R552S) suggesting this residue is a hotspot", and this residue has been shown to be structurally important (Lepri et al., 2011). Furthermore, missense variants in nearby residues (S548R, T549K, L550P) have been reported in the Human Gene Mutation Database in association with SOS1-related disorders (Stenson et al., 2014), further supporting the functional importance of this residue and this region of the protein.In summary, R552W in the SOS1 gene is interpreted as a disease-causing variant"

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Blueprint Genetics, SCV000927585.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 7, 2024

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