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

Clinical significance:Uncertain significance (Last evaluated: May 7, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000685882.1

Allele description [Variation Report for NM_005633.3(SOS1):c.1655G>T (p.Arg552Met)]

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

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_005633.3(SOS1):c.1655G>T (p.Arg552Met)
Other names:
NM_005633.3(SOS1):c.1655G>T
HGVS:
  • NC_000002.12:g.39022773C>A
  • NG_007530.1:g.102691G>T
  • NM_005633.3:c.1655G>T
  • NP_005624.2:p.Arg552Met
  • LRG_754t1:c.1655G>T
  • LRG_754:g.102691G>T
  • LRG_754p1:p.Arg552Met
  • NC_000002.11:g.39249914C>A
Protein change:
R552M
Links:
dbSNP: rs397517154
NCBI 1000 Genomes Browser:
rs397517154
Molecular consequence:
  • NM_005633.3:c.1655G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Rasopathy
Synonyms:
rasopathies; Noonan spectrum disorder
Identifiers:
MONDO: MONDO:0021060; MedGen: CN166718

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000813382Invitaecriteria provided, single submitter
Uncertain significance
(May 7, 2018)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod

Citations

PubMed

SOS1 mutations in Noonan syndrome: molecular spectrum, structural insights on pathogenic effects, and genotype-phenotype correlations.

Lepri F, De Luca A, Stella L, Rossi C, Baldassarre G, Pantaleoni F, Cordeddu V, Williams BJ, Dentici ML, Caputo V, Venanzi S, Bonaguro M, Kavamura I, Faienza MF, Pilotta A, Stanzial F, Faravelli F, Gabrielli O, Marino B, Neri G, Silengo MC, Ferrero GB, et al.

Hum Mutat. 2011 Jul;32(7):760-72. doi: 10.1002/humu.21492. Epub 2011 Apr 28.

PubMed [citation]
PMID:
21387466
PMCID:
PMC3118925

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000813382.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

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 moderate physicochemical difference between arginine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with Noonan syndrome (PMID: 21387466). ClinVar contains an entry for this variant (Variation ID: 40681). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). The p.Arg552 amino acid residue in SOS1 has been determined to be clinically significant (PMID: 21387466, 17143282, 23487764, 18854871, 17586837, 25073238, 21340158). This suggests that variants that disrupt this residue are likely to be causative of disease. 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.

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

Last Updated: Jun 14, 2021

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