NM_005633.3(SOS1):c.322G>A (p.Glu108Lys) AND not provided

Clinical significance:Pathogenic (Last evaluated: Aug 10, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000159144.3

Allele description [Variation Report for NM_005633.3(SOS1):c.322G>A (p.Glu108Lys)]

NM_005633.3(SOS1):c.322G>A (p.Glu108Lys)

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.322G>A (p.Glu108Lys)
Other names:
p.E108K:GAA>AAA; NM_005633.3(SOS1):c.322G>A
HGVS:
  • NC_000002.12:g.39058696C>T
  • NG_007530.1:g.66768G>A
  • NM_005633.3:c.322G>A
  • NP_005624.2:p.Glu108Lys
  • LRG_754t1:c.322G>A
  • LRG_754:g.66768G>A
  • LRG_754p1:p.Glu108Lys
  • NC_000002.11:g.39285837C>T
  • Q07889:p.Glu108Lys
  • c.322G>A
Protein change:
E108K
Links:
UniProtKB: Q07889#VAR_030423; dbSNP: rs397517164
NCBI 1000 Genomes Browser:
rs397517164
Molecular consequence:
  • NM_005633.3:c.322G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000209088GeneDxcriteria provided, single submitter
Pathogenic
(Aug 10, 2017)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000209088.10

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

Description

The E108K pathogenic variant in the SOS1 gene has been reported previously in association with Noonan syndrome (Tartaglia et al., 2007; Lepri et al., 2011). This variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position where amino acids with similar properties to Glutamic Acid are tolerated across species. However, the E108K variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Although in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function, functional studies demonstrate that the E108K variant, which is located in the histone fold domain of the encoded protein, disrupts protein activation and membrane assocation (Gureasko et al., 2010; Saliba et al., 2014). We interpret E108K as a pathogenic variant, consistent with global developmental delay, learning disability, pulmonic valve stenosis, pectus excavatum, hypertelorism, and easy bruising.

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

Last Updated: Sep 6, 2021

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