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NM_005633.4(SOS1):c.3709C>G (p.Pro1237Ala) AND Noonan syndrome

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Oct 7, 2020
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:
RCV001261115.4

Allele description [Variation Report for NM_005633.4(SOS1):c.3709C>G (p.Pro1237Ala)]

NM_005633.4(SOS1):c.3709C>G (p.Pro1237Ala)

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.3709C>G (p.Pro1237Ala)
HGVS:
  • NC_000002.12:g.38986117G>C
  • NG_007530.1:g.139347C>G
  • NM_001382394.1:c.3688C>G
  • NM_001382395.1:c.3664C>G
  • NM_005633.4:c.3709C>GMANE SELECT
  • NP_001369323.1:p.Pro1230Ala
  • NP_001369324.1:p.Pro1222Ala
  • NP_005624.2:p.Pro1237Ala
  • NP_005624.2:p.Pro1237Ala
  • LRG_754t1:c.3709C>G
  • LRG_754:g.139347C>G
  • LRG_754p1:p.Pro1237Ala
  • NC_000002.11:g.39213258G>C
  • NM_005633.3:c.3709C>G
Protein change:
P1222A
Links:
dbSNP: rs371408734
NCBI 1000 Genomes Browser:
rs371408734
Molecular consequence:
  • NM_001382394.1:c.3688C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382395.1:c.3664C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_005633.4:c.3709C>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
2

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
SCV001438522Service de Génétique Moléculaire, Hôpital Robert Debré
no assertion criteria provided
Uncertain significanceunknownclinical testing

SCV001450727St. Jude Molecular Pathology, St. Jude Children's Research Hospital
criteria provided, single submitter

(St. Jude Assertion Criteria 2020)		Uncertain significance
(Oct 7, 2020) 		germlineclinical testing

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownyesnot provided2not providednot providednot providedclinical testing

Details of each submission

From Service de Génétique Moléculaire, Hôpital Robert Debré, SCV001438522.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providednot providednot providednot providednot provided2not provided

From St. Jude Molecular Pathology, St. Jude Children's Research Hospital, SCV001450727.1

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

Description

The SOS1 c.3709C>G (p.Pro1237Ala) missense change has a maximum subpopulation frequency of 0.012% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/variant/2-39213258-G-C). In silico tools are not in agreement about a tolerated or damaging effect on the gene or protein product and functional studies have not been performed. To our knowledge, this variant has not been reported in individuals with Noonan syndrome (literature review and internal data). A different missense change at the same amino acid residue, c.3709C>A (p.Pro1237Thr), has been determined to be likely benign by the ClinGen RASopathy Variant Curation Expert Panel (ClinVar Accession: SCV000616503.3). In summary, this variant does not meet any of the ACMG/AMP criteria and is thus classified as of uncertain significance.

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

Last Updated: Sep 29, 2024