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NM_005633.3(SOS1):c.1655G>T (p.Arg552Met)

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Interpretation:
Likely pathogenic​

Review status:
reviewed by expert panel FDA Recognized Database
Submissions:
4 (Most recent: May 26, 2021)
Last evaluated:
May 10, 2019
Accession:
VCV000040681.4
Variation ID:
40681
Description:
single nucleotide variant
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NM_005633.3(SOS1):c.1655G>T (p.Arg552Met)

Allele ID
49151
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
2p22.1
Genomic location
2: 39022773 (GRCh38) GRCh38 UCSC
2: 39249914 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000002.12:g.39022773C>A
NC_000002.11:g.39249914C>A
NM_005633.3:c.1655G>T NP_005624.2:p.Arg552Met missense
... more HGVS
Protein change
R552M
Other names
NM_005633.3(SOS1):c.1655G>T
Canonical SPDI
NC_000002.12:39022772:C:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00000
Links
ClinGen: CA16616762
dbSNP: rs397517154
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely pathogenic 1 reviewed by expert panel May 10, 2019 RCV000787996.1
Pathogenic 2 criteria provided, multiple submitters, no conflicts Mar 23, 2021 RCV000484403.2
Uncertain significance 1 criteria provided, single submitter May 7, 2018 RCV000685882.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
SOS1 No evidence available No evidence available GRCh38
GRCh37
748 781

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(May 10, 2019)
reviewed by expert panel
Method: curation
Noonan syndrome and Noonan-related syndrome
(Autosomal dominant inheritance)
Allele origin: germline
ClinGen RASopathy Variant Curation Expert Panel
FDA Recognized Database
Accession: SCV000927025.1
Submitted: (Jul 15, 2019)
Evidence details
Publications
PubMed (2)
Other databases
https://erepo.clinicalgenome.org…
Comment:
The c.1655G>T (p.Arg552Met) variant has been identified in at least 3 independent occurrences in patients with clinical features of a RASopathy (PS4_Moderate; GeneDx internal data; … (more)
Uncertain significance
(May 07, 2018)
criteria provided, single submitter
Method: clinical testing
Rasopathy
Allele origin: germline
Invitae
Accession: SCV000813382.1
Submitted: (Aug 29, 2018)
Evidence details
Publications
PubMed (2)
Comment:
This sequence change replaces arginine with methionine at codon 552 of the SOS1 protein (p.Arg552Met). The arginine residue is highly conserved and there is a … (more)
Pathogenic
(Feb 09, 2017)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000565586.5
Submitted: (Jan 29, 2019)
Evidence details
Comment:
The R552M variant has been published previously in association with Noonan syndrome (Lepri et al., 2011). The variant is not observed in large population cohorts … (more)
Pathogenic
(Mar 23, 2021)
criteria provided, single submitter
Method: clinical testing
Not provided
Allele origin: germline
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV001715446.1
Submitted: (May 26, 2021)
Evidence details
Publications
PubMed (3)
Comment:
PS4, PM1_Strong, PP2, PP3

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Molecular and phenotypic spectrum of Noonan syndrome in Chinese patients. Li X Clinical genetics 2019 PMID: 31219622
Dermatological manifestations in Noonan syndrome: a prospective multicentric study of 129 patients positive for mutation. Bessis D The British journal of dermatology 2019 PMID: 30417923
Oncogenic Signaling Pathways in The Cancer Genome Atlas. Sanchez-Vega F Cell 2018 PMID: 29625050
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
SOS1 mutations in Noonan syndrome: molecular spectrum, structural insights on pathogenic effects, and genotype-phenotype correlations. Lepri F Human mutation 2011 PMID: 21387466
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/b58990d7-5f0e-4d39-bc5c-0202598cfebe - - - -

Text-mined citations for rs397517154...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jun 14, 2021