NM_002880.4(RAF1):c.683C>G (p.Ser228Cys) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 26, 2020
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:: RCV002362924.2

Allele description [Variation Report for NM_002880.4(RAF1):c.683C>G (p.Ser228Cys)]

NM_002880.4(RAF1):c.683C>G (p.Ser228Cys)

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.683C>G (p.Ser228Cys)

HGVS:

NC_000003.12:g.12604287G>C
NG_007467.1:g.64893C>G
NM_001354689.3:c.683C>G
NM_001354690.3:c.683C>G
NM_001354691.3:c.440C>G
NM_001354692.3:c.440C>G
NM_001354693.3:c.584C>G
NM_001354694.3:c.440C>G
NM_001354695.3:c.341C>G
NM_002880.4:c.683C>GMANE SELECT
NP_001341618.1:p.Ser228Cys
NP_001341619.1:p.Ser228Cys
NP_001341620.1:p.Ser147Cys
NP_001341621.1:p.Ser147Cys
NP_001341622.1:p.Ser195Cys
NP_001341623.1:p.Ser147Cys
NP_001341624.1:p.Ser114Cys
NP_002871.1:p.Ser228Cys
NP_002871.1:p.Ser228Cys
LRG_413t1:c.683C>G
LRG_413t2:c.683C>G
LRG_413:g.64893C>G
LRG_413p1:p.Ser228Cys
LRG_413p2:p.Ser228Cys
NC_000003.11:g.12645786G>C
NM_002880.3:c.683C>G
NR_148940.3:n.1014C>G
NR_148941.3:n.1014C>G
NR_148942.3:n.1014C>G

Protein change:

S114C

Links:

dbSNP: rs766437069

NCBI 1000 Genomes Browser:

rs766437069

Molecular consequence:

NM_001354689.3:c.683C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354690.3:c.683C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354691.3:c.440C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354692.3:c.440C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354693.3:c.584C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354694.3:c.440C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354695.3:c.341C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_002880.4:c.683C>G - missense variant - [Sequence Ontology: SO:0001583]
NR_148940.3:n.1014C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148941.3:n.1014C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148942.3:n.1014C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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LOC100840604 [Brachypodium distachyon]
LOC100840604 [Brachypodium distachyon]
Gene ID:100840604

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002666651	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Feb 26, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002666651

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Feb 26, 2020)

germline

clinical testing

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

Citation Link

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

Whole-Exome Sequencing Identifies Novel Heterozygous Mutation in RAF1 in Family With Neonatal Testicular Torsion.

Kohn TP, Lopategui DM, Arora H, Griswold AJ, Ramasamy R.

Urology. 2019 Jul;129:60-67. doi: 10.1016/j.urology.2019.01.052. Epub 2019 Mar 21.

PubMed [citation]

PMID:: 30904638

Details of each submission

From Ambry Genetics, SCV002666651.2

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

Description

The p.S228C variant (also known as c.683C>G), located in coding exon 6 of the RAF1 gene, results from a C to G substitution at nucleotide position 683. The serine at codon 228 is replaced by cysteine, an amino acid with dissimilar properties. This variant was detected in affected individuals in a family with testicular torsion and cryptorchidism, and biopsy of testicular tissue from an affected individual indicated reduced Raf-1 and pERK protein expression (Kohn TP et al. Urology, 2019 07;129:60-67). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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: May 1, 2024

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