NM_005633.4(SOS1):c.1820T>C (p.Ile607Thr) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Sep 9, 2016
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:: RCV000589437.5

Allele description [Variation Report for NM_005633.4(SOS1):c.1820T>C (p.Ile607Thr)]

NM_005633.4(SOS1):c.1820T>C (p.Ile607Thr)

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.1820T>C (p.Ile607Thr)

HGVS:

NC_000002.12:g.39022608A>G
NG_007530.1:g.102856T>C
NM_001382394.1:c.1799T>C
NM_001382395.1:c.1820T>C
NM_005633.4:c.1820T>CMANE SELECT
NP_001369323.1:p.Ile600Thr
NP_001369324.1:p.Ile607Thr
NP_005624.2:p.Ile607Thr
NP_005624.2:p.Ile607Thr
LRG_754t1:c.1820T>C
LRG_754:g.102856T>C
LRG_754p1:p.Ile607Thr
NC_000002.11:g.39249749A>G
NM_005633.3:c.1820T>C

Protein change:

I600T

Links:

dbSNP: rs758699499

NCBI 1000 Genomes Browser:

rs758699499

Molecular consequence:

NM_001382394.1:c.1799T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382395.1:c.1820T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_005633.4:c.1820T>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000344629	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Uncertain significance (Sep 9, 2016)	germline	clinical testing	Citation Link,
SCV000698619	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (May 23, 2016)	germline	clinical testing	LabCorp Variant Classification Summary - May 2015.docx Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000344629

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Uncertain significance
(Sep 9, 2016)

germline

clinical testing

Citation Link,

SCV000698619

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(May 23, 2016)

germline

clinical testing

LabCorp Variant Classification Summary - May 2015.docx

Citation Link

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

Details of each submission

From Eurofins Ntd Llc (ga), SCV000344629.4

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000698619.1

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

Description

Variant summary: The SOS1 c.1820T>C (p.Ile607Thr) variant causes a missense change involving a highly conserved nucleotide with 2/4 in silico tools (SNPs&GO not captured due to low reliability index) predicting a benign outcome, although these predictions have yet to be functionally assessed. This variant was observed in the large, broad control population, ExAC, with an allele frequency of 2/120916 (1/60458, frequency: 0.0000165), which does not exceed the estimated maximal expected allele frequency for a pathogenic SOS1 variant of 1/33333(0.00003) but does not rule out a possibility for it to be a rare functional polymorphism. The fact that c.1820T>C co-occurred with a known pathogenic variant in PTPN1 gene suggest a non-contributory role of the variant of interest. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories. Due to the absence of clinical information and lack of functional studies, the variant has been classified as a "Variant of Uncertain Significance (VUS)," until additional information becomes available.

#	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: Feb 25, 2025

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