NM_001354689.3(RAF1):c.1532C>G (p.Thr511Arg) AND not provided

Clinical significance:Likely pathogenic (Last evaluated: Jun 18, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000680803.1

Allele description [Variation Report for NM_001354689.3(RAF1):c.1532C>G (p.Thr511Arg)]

NM_001354689.3(RAF1):c.1532C>G (p.Thr511Arg)

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.1532C>G (p.Thr511Arg)
HGVS:
  • NC_000003.12:g.12585745G>C
  • NG_007467.1:g.83435C>G
  • NM_001354689.3:c.1532C>GMANE SELECT
  • NM_001354690.2:c.1472C>G
  • NM_001354691.2:c.1229C>G
  • NM_001354692.2:c.1229C>G
  • NM_001354693.2:c.1373C>G
  • NM_001354694.2:c.1289C>G
  • NM_001354695.2:c.1130C>G
  • NM_002880.3:c.1472C>G
  • NP_001341618.1:p.Thr511Arg
  • NP_001341619.1:p.Thr491Arg
  • NP_001341620.1:p.Thr410Arg
  • NP_001341621.1:p.Thr410Arg
  • NP_001341622.1:p.Thr458Arg
  • NP_001341623.1:p.Thr430Arg
  • NP_001341624.1:p.Thr377Arg
  • NP_002871.1:p.Thr491Arg
  • LRG_413t1:c.1472C>G
  • LRG_413t2:c.1532C>G
  • LRG_413:g.83435C>G
  • LRG_413p1:p.Thr491Arg
  • LRG_413p2:p.Thr511Arg
  • NC_000003.11:g.12627244G>C
  • NR_148940.2:n.1916C>G
  • NR_148941.2:n.1862C>G
  • NR_148942.2:n.1801C>G
  • P04049:p.Thr491Arg
Protein change:
T377R; THR491ARG
Links:
UniProtKB: P04049#VAR_037819; OMIM: 164760.0003; dbSNP: rs80338799
NCBI 1000 Genomes Browser:
rs80338799
Molecular consequence:
  • NM_001354689.3:c.1532C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354690.2:c.1472C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354691.2:c.1229C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354692.2:c.1229C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354693.2:c.1373C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354694.2:c.1289C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354695.2:c.1130C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002880.3:c.1472C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148940.2:n.1916C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148941.2:n.1862C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148942.2:n.1801C>G - 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
SCV000808247GeneDxcriteria provided, single submitter
Likely pathogenic
(Jun 18, 2018)
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, SCV000808247.1

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

Description

The T491R variant has been published previously in association with Noonan syndrome (Pandit et al., 2007). The variant is not observed in large population cohorts (Lek et al., 2016). T491R is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Missense variants in the same residue (T491I) and in nearby residues (D486N/G, L489F) have been reported by the Human Gene Mutation Database and/or GeneDx 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; however, the possibility that it is benign cannot be excluded.

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

Last Updated: Oct 8, 2021

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