NM_001354689.3(RAF1):c.995T>C (p.Val332Ala) AND Rasopathy

Clinical significance:Uncertain significance (Last evaluated: Apr 3, 2017)

Review status:3 stars out of maximum of 4 stars

reviewed by expert panel

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000471101.6

Allele description [Variation Report for NM_001354689.3(RAF1):c.995T>C (p.Val332Ala)]

NM_001354689.3(RAF1):c.995T>C (p.Val332Ala)

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.995T>C (p.Val332Ala)
Other names:
p.V312A:GTG>GCG; NM_002880.3(RAF1):c.935T>C
HGVS:
  • NC_000003.12:g.12600207A>G
  • NG_007467.1:g.68973T>C
  • NM_001354689.3:c.995T>CMANE SELECT
  • NM_001354690.2:c.935T>C
  • NM_001354691.2:c.692T>C
  • NM_001354692.2:c.692T>C
  • NM_001354693.2:c.836T>C
  • NM_001354694.2:c.752T>C
  • NM_001354695.2:c.593T>C
  • NM_002880.3:c.935T>C
  • NP_001341618.1:p.Val332Ala
  • NP_001341619.1:p.Val312Ala
  • NP_001341620.1:p.Val231Ala
  • NP_001341621.1:p.Val231Ala
  • NP_001341622.1:p.Val279Ala
  • NP_001341623.1:p.Val251Ala
  • NP_001341624.1:p.Val198Ala
  • NP_002871.1:p.Val312Ala
  • LRG_413t1:c.935T>C
  • LRG_413t2:c.995T>C
  • LRG_413:g.68973T>C
  • LRG_413p1:p.Val312Ala
  • LRG_413p2:p.Val332Ala
  • NC_000003.11:g.12641706A>G
  • NR_148940.2:n.1266T>C
  • NR_148941.2:n.1266T>C
  • NR_148942.2:n.1266T>C
Protein change:
V198A
Links:
dbSNP: rs370243307
NCBI 1000 Genomes Browser:
rs370243307
Molecular consequence:
  • NM_001354689.3:c.995T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354690.2:c.935T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354691.2:c.692T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354692.2:c.692T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354693.2:c.836T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354694.2:c.752T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354695.2:c.593T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002880.3:c.935T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148940.2:n.1266T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148941.2:n.1266T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148942.2:n.1266T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV000552094Invitaecriteria provided, single submitter
Likely benign
(Nov 2, 2020)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV000616424ClinGen RASopathy Variant Curation Expert Panelreviewed by expert panel
Uncertain significance
(Apr 3, 2017)
germlinecuration

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing, curation

Citations

PubMed

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, SCV000552094.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From ClinGen RASopathy Variant Curation Expert Panel, SCV000616424.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The c.935T>C p.Val312Ala variant has been identified in 2 probands with clinical features of RASopathies (PS4 not met; GeneDx, Partners LMM internal data; GTR ID's: 26957, 21766; ClinVar SCV000200036.4; SCV000209006.12). Computational prediction tools and conservation analysis suggest that the p.Val312Ala variant does not impact the protein (BP4). In summary, the clinical significance of the p.Val312Ala variant is uncertain. RASopathy-specific ACMG/AMP criteria applied (PMID:29493581): BP4.

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

Last Updated: Aug 27, 2021

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