NM_001354689.3(RAF1):c.779C>T (p.Thr260Ile) AND not provided

Clinical significance:Likely pathogenic (Last evaluated: May 5, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000494156.1

Allele description [Variation Report for NM_001354689.3(RAF1):c.779C>T (p.Thr260Ile)]

NM_001354689.3(RAF1):c.779C>T (p.Thr260Ile)

Gene:
RAF1:Raf-1 proto-oncogene, serine/threonine kinase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3p25.2
Genomic location:
Preferred name:
NM_001354689.3(RAF1):c.779C>T (p.Thr260Ile)
HGVS:
  • NC_000003.12:g.12604191G>A
  • NG_007467.1:g.64989C>T
  • NM_001354689.3:c.779C>TMANE SELECT
  • NM_001354690.2:c.779C>T
  • NM_001354691.2:c.536C>T
  • NM_001354692.2:c.536C>T
  • NM_001354693.2:c.680C>T
  • NM_001354694.2:c.536C>T
  • NM_001354695.2:c.437C>T
  • NM_002880.3:c.779C>T
  • NP_001341618.1:p.Thr260Ile
  • NP_001341619.1:p.Thr260Ile
  • NP_001341620.1:p.Thr179Ile
  • NP_001341621.1:p.Thr179Ile
  • NP_001341622.1:p.Thr227Ile
  • NP_001341623.1:p.Thr179Ile
  • NP_001341624.1:p.Thr146Ile
  • NP_002871.1:p.Thr260Ile
  • LRG_413t1:c.779C>T
  • LRG_413t2:c.779C>T
  • LRG_413:g.64989C>T
  • LRG_413p1:p.Thr260Ile
  • LRG_413p2:p.Thr260Ile
  • NC_000003.11:g.12645690G>A
  • NM_002880.3(RAF1):c.779C>T
  • NR_148940.2:n.1110C>T
  • NR_148941.2:n.1110C>T
  • NR_148942.2:n.1110C>T
  • P04049:p.Thr260Ile
Protein change:
T146I
Links:
UniProtKB: P04049#VAR_037810; dbSNP: rs869025501
NCBI 1000 Genomes Browser:
rs869025501
Molecular consequence:
  • NM_001354689.3:c.779C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354690.2:c.779C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354691.2:c.536C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354692.2:c.536C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354693.2:c.680C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354694.2:c.536C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354695.2:c.437C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002880.3:c.779C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148940.2:n.1110C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148941.2:n.1110C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148942.2:n.1110C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000582743GeneDxcriteria provided, single submitter
Likely pathogenic
(May 5, 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, SCV000582743.4

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

Description

The T260I variant has been published in a patient diagnosed with hypertrophic cardiomyopathy (HCM) (Pandit et al., 2007) with limited evidence. The T260I variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The T260I 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. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in the same (T260R) and in nearby residues (R256S, S257L, S259P/T/F, P261S/A/T/R/L, N262K/K) have been reported in the Human Gene Mutation Database in association with Noonan syndrome (Stenson et al., 2014), supporting the functional importance of this region of the protein. In summary, this variant is likely pathogenic.

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

Last Updated: Aug 27, 2021

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