NM_005633.4(SOS1):c.1655G>T (p.Arg552Met) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jul 21, 2024
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:: RCV000484403.9

Allele description [Variation Report for NM_005633.4(SOS1):c.1655G>T (p.Arg552Met)]

NM_005633.4(SOS1):c.1655G>T (p.Arg552Met)

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.1655G>T (p.Arg552Met)

Other names:

NM_005633.3(SOS1):c.1655G>T

HGVS:

NC_000002.12:g.39022773C>A
NG_007530.1:g.102691G>T
NM_001382394.1:c.1634G>T
NM_001382395.1:c.1655G>T
NM_005633.4:c.1655G>TMANE SELECT
NP_001369323.1:p.Arg545Met
NP_001369324.1:p.Arg552Met
NP_005624.2:p.Arg552Met
NP_005624.2:p.Arg552Met
LRG_754t1:c.1655G>T
LRG_754:g.102691G>T
LRG_754p1:p.Arg552Met
NC_000002.11:g.39249914C>A
NC_000002.11:g.39249914C>A
NM_005633.3:c.1655G>T

Protein change:

R545M

Links:

dbSNP: rs397517154

NCBI 1000 Genomes Browser:

rs397517154

Molecular consequence:

NM_001382394.1:c.1634G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382395.1:c.1655G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_005633.4:c.1655G>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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hypothetical protein AURANDRAFT_52346 [Aureococcus anophagefferens]
hypothetical protein AURANDRAFT_52346 [Aureococcus anophagefferens]
gi|676379975|ref|XP_009033266.1||gn _WGS:ACJI|AURANDRAFT_52346

Protein
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
SCV000565586	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jul 21, 2024)	germline	clinical testing	Citation Link,
SCV001715446	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ClinGen RASopathy ACMG Specifications v1)	Pathogenic (Mar 23, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 21387466, 30417923, 31219622, 29493581

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000565586

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jul 21, 2024)

germline

clinical testing

Citation Link,

SCV001715446

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ClinGen RASopathy ACMG Specifications v1)

Pathogenic
(Mar 23, 2021)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

SOS1 mutations in Noonan syndrome: molecular spectrum, structural insights on pathogenic effects, and genotype-phenotype correlations.

Lepri F, De Luca A, Stella L, Rossi C, Baldassarre G, Pantaleoni F, Cordeddu V, Williams BJ, Dentici ML, Caputo V, Venanzi S, Bonaguro M, Kavamura I, Faienza MF, Pilotta A, Stanzial F, Faravelli F, Gabrielli O, Marino B, Neri G, Silengo MC, Ferrero GB, et al.

Hum Mutat. 2011 Jul;32(7):760-72. doi: 10.1002/humu.21492. Epub 2011 Apr 28.

PubMed [citation]

PMID:: 21387466
PMCID:: PMC3118925

Dermatological manifestations in Noonan syndrome: a prospective multicentric study of 129 patients positive for mutation.

Bessis D, Miquel J, Bourrat E, Chiaverini C, Morice-Picard F, Abadie C, Manna F, Baumann C, Best M, Blanchet P, Bursztejn AC, Capri Y, Coubes C, Giuliano F, Guillaumont S, Hadj-Rabia S, Jacquemont ML, Jeandel C, Lacombe D, Mallet S, Mazereeuw-Hautier J, Molinari N, et al.

Br J Dermatol. 2019 Jun;180(6):1438-1448. doi: 10.1111/bjd.17404. Epub 2019 Jan 18.

PubMed [citation]

PMID:: 30417923

See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV000565586.8

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

Description

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24803665, 30417923, 31219622, 20648242, 29493581, 17143282, 21387466, 12628188)

#	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 Mayo Clinic Laboratories, Mayo Clinic, SCV001715446.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (4)

Description

PS4, PM1_Strong, PP2, PP3

#	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		1	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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