NM_002880.4(RAF1):c.974A>C (p.Gln325Pro) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 18, 2023
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:: RCV004022166.1

Allele description [Variation Report for NM_002880.4(RAF1):c.974A>C (p.Gln325Pro)]

NM_002880.4(RAF1):c.974A>C (p.Gln325Pro)

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.974A>C (p.Gln325Pro)

HGVS:

NC_000003.12:g.12600168T>G
NG_007467.1:g.69012A>C
NM_001354689.3:c.1034A>C
NM_001354690.3:c.974A>C
NM_001354691.3:c.731A>C
NM_001354692.3:c.731A>C
NM_001354693.3:c.875A>C
NM_001354694.3:c.791A>C
NM_001354695.3:c.632A>C
NM_002880.4:c.974A>CMANE SELECT
NP_001341618.1:p.Gln345Pro
NP_001341619.1:p.Gln325Pro
NP_001341620.1:p.Gln244Pro
NP_001341621.1:p.Gln244Pro
NP_001341622.1:p.Gln292Pro
NP_001341623.1:p.Gln264Pro
NP_001341624.1:p.Gln211Pro
NP_002871.1:p.Gln325Pro
NP_002871.1:p.Gln325Pro
LRG_413t1:c.974A>C
LRG_413t2:c.1034A>C
LRG_413:g.69012A>C
LRG_413p1:p.Gln325Pro
LRG_413p2:p.Gln345Pro
NC_000003.11:g.12641667T>G
NM_002880.3:c.974A>C
NR_148940.3:n.1305A>C
NR_148941.3:n.1305A>C
NR_148942.3:n.1305A>C

Protein change:

Q211P

Links:

dbSNP: rs764719098

NCBI 1000 Genomes Browser:

rs764719098

Molecular consequence:

NM_001354689.3:c.1034A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354690.3:c.974A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354691.3:c.731A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354692.3:c.731A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354693.3:c.875A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354694.3:c.791A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354695.3:c.632A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_002880.4:c.974A>C - missense variant - [Sequence Ontology: SO:0001583]
NR_148940.3:n.1305A>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148941.3:n.1305A>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148942.3:n.1305A>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005019572	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Dec 18, 2023)	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

SCV005019572

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Dec 18, 2023)

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

Alpha-protein kinase 3 (ALPK3) truncating variants are a cause of autosomal dominant hypertrophic cardiomyopathy.

Lopes LR, Garcia-Hernández S, Lorenzini M, Futema M, Chumakova O, Zateyshchikov D, Isidoro-Garcia M, Villacorta E, Escobar-Lopez L, Garcia-Pavia P, Bilbao R, Dobarro D, Sandin-Fuentes M, Catalli C, Gener Querol B, Mezcua A, Garcia Pinilla J, Bloch Rasmussen T, Ferreira-Aguar A, Revilla-Martí P, Basurte Elorz MT, Bautista Paves A, et al.

Eur Heart J. 2021 Aug 21;42(32):3063-3073. doi: 10.1093/eurheartj/ehab424.

PubMed [citation]

PMID:: 34263907
PMCID:: PMC8380059

Details of each submission

From Ambry Genetics, SCV005019572.1

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

Description

The p.Q325P variant (also known as c.974A>C), located in coding exon 8 of the RAF1 gene, results from an A to C substitution at nucleotide position 974. The glutamine at codon 325 is replaced by proline, an amino acid with similar properties. This alteration has been reported in a pediatric cardiomyopathy cohort (Lopes LR et al. Eur Heart J, 2021 Aug;42:3063-3073). This amino acid position is highly 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 7, 2024

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