NM_002880.4(RAF1):c.1678A>C (p.Met560Leu) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 21, 2016
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:: RCV000418401.1

Allele description [Variation Report for NM_002880.4(RAF1):c.1678A>C (p.Met560Leu)]

NM_002880.4(RAF1):c.1678A>C (p.Met560Leu)

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.1678A>C (p.Met560Leu)

HGVS:

NC_000003.12:g.12584972T>G
NG_007467.1:g.84208A>C
NM_001354689.3:c.1738A>C
NM_001354690.3:c.1678A>C
NM_001354691.3:c.1435A>C
NM_001354692.3:c.1435A>C
NM_001354693.3:c.1579A>C
NM_001354694.3:c.1495A>C
NM_001354695.3:c.1336A>C
NM_002880.4:c.1678A>CMANE SELECT
NP_001341618.1:p.Met580Leu
NP_001341619.1:p.Met560Leu
NP_001341620.1:p.Met479Leu
NP_001341621.1:p.Met479Leu
NP_001341622.1:p.Met527Leu
NP_001341623.1:p.Met499Leu
NP_001341624.1:p.Met446Leu
NP_002871.1:p.Met560Leu
NP_002871.1:p.Met560Leu
LRG_413t1:c.1678A>C
LRG_413t2:c.1738A>C
LRG_413:g.84208A>C
LRG_413p1:p.Met560Leu
LRG_413p2:p.Met580Leu
NC_000003.11:g.12626471T>G
NM_002880.3:c.1678A>C
NR_148940.3:n.2122A>C
NR_148941.3:n.2068A>C
NR_148942.3:n.2007A>C

Protein change:

M446L

Links:

dbSNP: rs754942031

NCBI 1000 Genomes Browser:

rs754942031

Molecular consequence:

NM_001354689.3:c.1738A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354690.3:c.1678A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354691.3:c.1435A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354692.3:c.1435A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354693.3:c.1579A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354694.3:c.1495A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354695.3:c.1336A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_002880.4:c.1678A>C - missense variant - [Sequence Ontology: SO:0001583]
NR_148940.3:n.2122A>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148941.3:n.2068A>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148942.3:n.2007A>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: CN517202

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000535567	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Dec 21, 2016)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000535567

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Dec 21, 2016)

germline

clinical testing

Citation Link

Help

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000535567.5

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

Description

The M560L variant in the RAF1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The M560L 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. The M560L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, we interpret M560L as a variant of uncertain significance

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

Last Updated: Apr 23, 2022

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