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NM_005633.4(SOS1):c.3387C>T (p.Gly1129=) AND Noonan syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 12, 2021
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:
RCV001775112.3

Allele description [Variation Report for NM_005633.4(SOS1):c.3387C>T (p.Gly1129=)]

NM_005633.4(SOS1):c.3387C>T (p.Gly1129=)

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.3387C>T (p.Gly1129=)
HGVS:
  • NC_000002.12:g.38989274G>A
  • NG_007530.1:g.136190C>T
  • NM_001382394.1:c.3366C>T
  • NM_001382395.1:c.3347-1683C>T
  • NM_005633.4:c.3387C>TMANE SELECT
  • NP_001369323.1:p.Gly1122=
  • NP_005624.2:p.Gly1129=
  • NP_005624.2:p.Gly1129=
  • LRG_754t1:c.3387C>T
  • LRG_754:g.136190C>T
  • LRG_754p1:p.Gly1129=
  • NC_000002.11:g.39216415G>A
  • NM_005633.3:c.3387C>T
Links:
dbSNP: rs772823827
NCBI 1000 Genomes Browser:
rs772823827
Molecular consequence:
  • NM_001382395.1:c.3347-1683C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001382394.1:c.3366C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_005633.4:c.3387C>T - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:
Noonan syndrome (NS)
Synonyms:
Noonan's syndrome; Pseudo-Turner syndrome
Identifiers:
MONDO: MONDO:0018997; MeSH: D009634; MedGen: C0028326; OMIM: PS163950

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002012430St. Jude Molecular Pathology, St. Jude Children's Research Hospital
criteria provided, single submitter

(St. Jude Assertion Criteria 2020)		Uncertain significance
(Oct 12, 2021) 		germlineclinical testing

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From St. Jude Molecular Pathology, St. Jude Children's Research Hospital, SCV002012430.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The SOS1 c.3387C>T (p.Gly1129=) synonymous change has a maximum subpopulation frequency of 0.0070% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/variant/2-39216415-G-A?dataset=gnomad_r2_1). This frequency does not meet criteria for PM2 or BS1 as defined by the RASopathy Variant Curation Expert Panel (PMID:29493581). Algorithms that predict the impact of sequence changes on splicing indicate that this variant does not affect splicing (BP4). RNA data demonstrates skipping of exon 21 in approximately 30% of reads (internal data), however the functional significance of this consequence is currently unknown. To our knowledge, this variant has not been reported in individuals with Noonan syndrome. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria, as specified by the RASopathy Variant Curation Expert Panel (PMID:29493581): BP4.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 25, 2025