NM_000186.4(CFH):c.524G>C (p.Arg175Pro) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Feb 13, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000788638.4

Allele description

NM_000186.4(CFH):c.524G>C (p.Arg175Pro)

Gene:

CFH:complement factor H [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q31.3

Genomic location:

Preferred name:

NM_000186.4(CFH):c.524G>C (p.Arg175Pro)

HGVS:

NC_000001.11:g.196677572G>C
NG_007259.1:g.30562G>C
NM_000186.4:c.524G>CMANE SELECT
NM_001014975.3:c.524G>C
NP_000177.2:p.Arg175Pro
NP_000177.2:p.Arg175Pro
NP_001014975.1:p.Arg175Pro
LRG_47t1:c.524G>C
LRG_47:g.30562G>C
LRG_47p1:p.Arg175Pro
NC_000001.10:g.196646702G>C
NM_000186.3:c.524G>C

Protein change:

R175P

Links:

dbSNP: rs139360826

NCBI 1000 Genomes Browser:

rs139360826

Molecular consequence:

NM_000186.4:c.524G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001014975.3:c.524G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000927825	Blueprint Genetics	criteria provided, single submitter (Blueprint Genetics Variant Classification Scheme)	Uncertain significance (Jul 26, 2018)	germline	clinical testing	Citation Link,
SCV003524009	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 13, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 26501415, 27572114, 34189567, 36445700, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000927825

Blueprint Genetics

criteria provided, single submitter

(Blueprint Genetics Variant Classification Scheme)

Uncertain significance
(Jul 26, 2018)

germline

clinical testing

Citation Link,

SCV003524009

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 13, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

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

Rare Variants in the Functional Domains of Complement Factor H Are Associated With Age-Related Macular Degeneration.

Triebwasser MP, Roberson ED, Yu Y, Schramm EC, Wagner EK, Raychaudhuri S, Seddon JM, Atkinson JP.

Invest Ophthalmol Vis Sci. 2015 Oct;56(11):6873-8. doi: 10.1167/iovs.15-17432.

PubMed [citation]

PMID:: 26501415
PMCID:: PMC4627248

Mapping rare, deleterious mutations in Factor H: Association with early onset, drusen burden, and lower antigenic levels in familial AMD.

Wagner EK, Raychaudhuri S, Villalonga MB, Java A, Triebwasser MP, Daly MJ, Atkinson JP, Seddon JM.

Sci Rep. 2016 Aug 30;6:31531. doi: 10.1038/srep31531.

PubMed [citation]

PMID:: 27572114
PMCID:: PMC5004131

See all PubMed Citations (5)

Details of each submission

From Blueprint Genetics, SCV000927825.1

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

#	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

From Invitae, SCV003524009.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 175 of the CFH protein (p.Arg175Pro). This variant is present in population databases (rs139360826, gnomAD 0.007%). This missense change has been observed in individual(s) with age-related macular degeneration (PMID: 26501415, 27572114). ClinVar contains an entry for this variant (Variation ID: 636726). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change affects CFH function (PMID: 27572114, 34189567, 36445700). 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: May 7, 2024

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