NM_005633.4(SOS1):c.3322G>C (p.Asp1108His) AND RASopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 13, 2022
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:: RCV002532351.3

Allele description [Variation Report for NM_005633.4(SOS1):c.3322G>C (p.Asp1108His)]

NM_005633.4(SOS1):c.3322G>C (p.Asp1108His)

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.3322G>C (p.Asp1108His)

HGVS:

NC_000002.12:g.38995147C>G
NG_007530.1:g.130317G>C
NM_001382394.1:c.3301G>C
NM_001382395.1:c.3322G>C
NM_005633.4:c.3322G>CMANE SELECT
NP_001369323.1:p.Asp1101His
NP_001369324.1:p.Asp1108His
NP_005624.2:p.Asp1108His
NP_005624.2:p.Asp1108His
LRG_754t1:c.3322G>C
LRG_754:g.130317G>C
LRG_754p1:p.Asp1108His
NC_000002.11:g.39222288C>G
NM_005633.3:c.3322G>C

Protein change:

D1101H

Links:

dbSNP: rs199856844

NCBI 1000 Genomes Browser:

rs199856844

Molecular consequence:

NM_001382394.1:c.3301G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382395.1:c.3322G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_005633.4:c.3322G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: RASopathy
Synonyms:: rasopathies; Noonan spectrum disorder
Identifiers:: MONDO: MONDO:0021060; MedGen: C5555857

Recent activity

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AL646749 XGC-neurula Xenopus tropicalis cDNA clone TNeu029j17 5', mRNA sequence
AL646749 XGC-neurula Xenopus tropicalis cDNA clone TNeu029j17 5', mRNA sequence
gi|38222979|gnl|dbEST|20325518|emb| 749.2|

Nucleotide
Profile neighbors for GEO Profiles (Select 55723765) (199)
GEO Profiles
Chromosome neighbors for GEO Profiles (Select 55758267) (20)
GEO Profiles
OMIM Links for GEO Profiles (Select 55771708) (1)
OMIM
SLC6A13 solute carrier family 6 member 13 [Homo sapiens]
SLC6A13 solute carrier family 6 member 13 [Homo sapiens]
Gene ID:6540

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003463072	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 13, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29907801, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003463072

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 13, 2022)

germline

clinical testing

PubMed (2)
[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	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Comparative assessment of gene-specific variant distribution in prenatal and postnatal cohorts tested for Noonan syndrome and related conditions.

Leach NT, Wilson Mathews DR, Rosenblum LS, Zhou Z, Zhu H, Heim RA.

Genet Med. 2019 Feb;21(2):417-425. doi: 10.1038/s41436-018-0062-0. Epub 2018 Jun 15. Erratum in: Genet Med. 2019 Jul;21(7):1670. doi: 10.1038/s41436-018-0128-z.

PubMed [citation]

PMID:: 29907801

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, SCV003463072.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 496304). This missense change has been observed in individual(s) with clinical features of SOS1-related conditions (PMID: 29907801). This variant is present in population databases (rs199856844, gnomAD 0.0009%). This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 1108 of the SOS1 protein (p.Asp1108His).

#	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

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