NM_172351.3(CD46):c.692C>G (p.Pro231Arg) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Sep 21, 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:: RCV001507532.8

Allele description [Variation Report for NM_172351.3(CD46):c.692C>G (p.Pro231Arg)]

NM_172351.3(CD46):c.692C>G (p.Pro231Arg)

Gene:

CD46:CD46 molecule [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q32.2

Genomic location:

Preferred name:

NM_172351.3(CD46):c.692C>G (p.Pro231Arg)

HGVS:

NC_000001.11:g.207767031C>G
NG_009296.1:g.19975C>G
NM_002389.4:c.692C>G
NM_153826.4:c.692C>G
NM_172350.3:c.692C>G
NM_172351.3:c.692C>GMANE SELECT
NM_172352.3:c.692C>G
NM_172353.3:c.692C>G
NM_172355.3:c.692C>G
NM_172356.3:c.692C>G
NM_172357.3:c.692C>G
NM_172358.3:c.692C>G
NM_172359.3:c.692C>G
NM_172361.3:c.692C>G
NP_002380.3:p.Pro231Arg
NP_722548.1:p.Pro231Arg
NP_758860.1:p.Pro231Arg
NP_758861.1:p.Pro231Arg
NP_758862.1:p.Pro231Arg
NP_758863.1:p.Pro231Arg
NP_758865.1:p.Pro231Arg
NP_758866.1:p.Pro231Arg
NP_758867.1:p.Pro231Arg
NP_758868.1:p.Pro231Arg
NP_758869.1:p.Pro231Arg
NP_758871.1:p.Pro231Arg
LRG_155t1:c.692C>G
LRG_155:g.19975C>G
LRG_155p1:p.Pro231Arg
NC_000001.10:g.207940376C>G
p.Pro231Arg

Protein change:

P231R

Links:

dbSNP: rs1271761432

NCBI 1000 Genomes Browser:

rs1271761432

Molecular consequence:

NM_002389.4:c.692C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_153826.4:c.692C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172350.3:c.692C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172351.3:c.692C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172352.3:c.692C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172353.3:c.692C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172355.3:c.692C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172356.3:c.692C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172357.3:c.692C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172358.3:c.692C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172359.3:c.692C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172361.3:c.692C>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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
SCV001713132	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 16, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20513133, 24029428, 25741868
SCV003524003	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 21, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20513133, 24029428, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001713132

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 16, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV003524003

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 21, 2023)

germline

clinical testing

PubMed (3)
[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	2	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Mutations in alternative pathway complement proteins in American patients with atypical hemolytic uremic syndrome.

Maga TK, Nishimura CJ, Weaver AE, Frees KL, Smith RJ.

Hum Mutat. 2010 Jun;31(6):E1445-60. doi: 10.1002/humu.21256.

PubMed [citation]

PMID:: 20513133

See all PubMed Citations (4)

Details of each submission

From Mayo Clinic Laboratories, Mayo Clinic, SCV001713132.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (3)

Description

PM2_supporting, PS4_supporting

#	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		2	not provided	not provided	not provided

From Invitae, SCV003524003.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

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. This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 231 of the CD46 protein (p.Pro231Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of atypical hemolytic uremic syndrome (PMID: 20513133, 24029428). ClinVar contains an entry for this variant (Variation ID: 1162906). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CD46 protein function.

#	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: Feb 20, 2024

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