NM_002880.4(RAF1):c.811C>A (p.Pro271Thr) AND RASopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 17, 2019
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001053964.7

Allele description [Variation Report for NM_002880.4(RAF1):c.811C>A (p.Pro271Thr)]

NM_002880.4(RAF1):c.811C>A (p.Pro271Thr)

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_002880.4(RAF1):c.811C>A (p.Pro271Thr)

HGVS:

NC_000003.12:g.12604159G>T
NG_007467.1:g.65021C>A
NM_001354689.3:c.811C>A
NM_001354690.3:c.811C>A
NM_001354691.3:c.568C>A
NM_001354692.3:c.568C>A
NM_001354693.3:c.712C>A
NM_001354694.3:c.568C>A
NM_001354695.3:c.469C>A
NM_002880.4:c.811C>AMANE SELECT
NP_001341618.1:p.Pro271Thr
NP_001341619.1:p.Pro271Thr
NP_001341620.1:p.Pro190Thr
NP_001341621.1:p.Pro190Thr
NP_001341622.1:p.Pro238Thr
NP_001341623.1:p.Pro190Thr
NP_001341624.1:p.Pro157Thr
NP_002871.1:p.Pro271Thr
NP_002871.1:p.Pro271Thr
LRG_413t1:c.811C>A
LRG_413t2:c.811C>A
LRG_413:g.65021C>A
LRG_413p1:p.Pro271Thr
LRG_413p2:p.Pro271Thr
NC_000003.11:g.12645658G>T
NM_002880.3:c.811C>A
NR_148940.3:n.1142C>A
NR_148941.3:n.1142C>A
NR_148942.3:n.1142C>A

Protein change:

P157T

Links:

dbSNP: rs1458313379

NCBI 1000 Genomes Browser:

rs1458313379

Molecular consequence:

NM_001354689.3:c.811C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354690.3:c.811C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354691.3:c.568C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354692.3:c.568C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354693.3:c.712C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354694.3:c.568C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354695.3:c.469C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002880.4:c.811C>A - missense variant - [Sequence Ontology: SO:0001583]
NR_148940.3:n.1142C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148941.3:n.1142C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148942.3:n.1142C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: RASopathy
Synonyms:: rasopathies; Noonan spectrum disorder
Identifiers:: MONDO: MONDO:0021060; MedGen: C5555857

Recent activity

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NUP155 nucleoporin 155 [Homo sapiens]
NUP155 nucleoporin 155 [Homo sapiens]
Gene ID:9631

Gene
9631[uid] AND (alive[prop]) (1)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001218254	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 17, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001218254

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 17, 2019)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001218254.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with RAF1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with threonine at codon 271 of the RAF1 protein (p.Pro271Thr). The proline residue is moderately conserved and there is a small physicochemical difference between proline and threonine. 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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