NM_000064.4(C3):c.3953T>G (p.Leu1318Arg) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 5, 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:: RCV001873534.4

Allele description [Variation Report for NM_000064.4(C3):c.3953T>G (p.Leu1318Arg)]

NM_000064.4(C3):c.3953T>G (p.Leu1318Arg)

Gene:

C3:complement C3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19p13.3

Genomic location:

Preferred name:

NM_000064.4(C3):c.3953T>G (p.Leu1318Arg)

HGVS:

NC_000019.10:g.6685004A>C
NG_009557.1:g.40648T>G
NM_000064.4:c.3953T>GMANE SELECT
NP_000055.2:p.Leu1318Arg
LRG_27t1:c.3953T>G
LRG_27:g.40648T>G
NC_000019.9:g.6685015A>C
NC_000019.9:g.6685015A>C
NM_000064.2:c.3953T>G

Protein change:

L1318R

Links:

dbSNP: rs769873702

NCBI 1000 Genomes Browser:

rs769873702

Molecular consequence:

NM_000064.4:c.3953T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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hypothetical protein OPI73_07330 [Pseudomonas aeruginosa]
hypothetical protein OPI73_07330 [Pseudomonas aeruginosa]
gi|2732009600|gnl|PRJNA899139|OPI73 0|gb|XAQ17512.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002279105	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 5, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26283675, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002279105

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 5, 2023)

germline

clinical testing

PubMed (2)
[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

High-Throughput Genetic Testing for Thrombotic Microangiopathies and C3 Glomerulopathies.

Bu F, Borsa NG, Jones MB, Takanami E, Nishimura C, Hauer JJ, Azaiez H, Black-Ziegelbein EA, Meyer NC, Kolbe DL, Li Y, Frees K, Schnieders MJ, Thomas C, Nester C, Smith RJ.

J Am Soc Nephrol. 2016 Apr;27(4):1245-53. doi: 10.1681/ASN.2015040385. Epub 2015 Aug 17.

PubMed [citation]

PMID:: 26283675
PMCID:: PMC4814193

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002279105.3

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

Description

This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1318 of the C3 protein (p.Leu1318Arg). This variant is present in population databases (rs769873702, gnomAD 0.04%). This missense change has been observed in individual(s) with C3-related conditions (PMID: 26283675). ClinVar contains an entry for this variant (Variation ID: 894696). 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 C3 protein function. 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: Sep 29, 2024

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