NM_172369.5(C1QC):c.100G>A (p.Gly34Arg) AND not provided

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

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 9, 2024
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:: RCV001200330.25

Allele description

NM_172369.5(C1QC):c.100G>A (p.Gly34Arg)

Gene:

C1QC:complement C1q C chain [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.12

Genomic location:

Preferred name:

NM_172369.5(C1QC):c.100G>A (p.Gly34Arg)

Other names:

C1QC, GLY6ARG; G6R

HGVS:

NC_000001.11:g.22644123G>A
NG_007565.1:g.5499G>A
NM_001114101.3:c.100G>A
NM_001347619.2:c.100G>A
NM_001347620.2:c.-87+409G>A
NM_172369.5:c.100G>AMANE SELECT
NP_001107573.1:p.Gly34Arg
NP_001334548.1:p.Gly34Arg
NP_758957.2:p.Gly34Arg
LRG_24:g.5499G>A
NC_000001.10:g.22970616G>A
NM_172369.4:c.100G>A

Note:

NCBI staff established the HGVS expression for this deletion based on review of the sequence in Figure 2 of the paper by Slingsby et al., 1996 (PubMed 8630118).

Protein change:

G34R; GLY6ARG

Links:

OMIM: 120575.0003; dbSNP: rs200206736

NCBI 1000 Genomes Browser:

rs200206736

Molecular consequence:

NM_001347620.2:c.-87+409G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001114101.3:c.100G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001347619.2:c.100G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_172369.5:c.100G>A - 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
SCV001371256	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Apr 1, 2020)	germline	clinical testing	Citation Link,
SCV002247271	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 9, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 7900940, 8630118, 28082982, 30008451, 31357913, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001371256

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Pathogenic
(Apr 1, 2020)

germline

clinical testing

Citation Link,

SCV002247271

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 9, 2024)

germline

clinical testing

PubMed (6)
[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	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Complete functional C1q deficiency associated with systemic lupus erythematosus (SLE).

Kirschfink M, Petry F, Khirwadkar K, Wigand R, Kaltwasser JP, Loos M.

Clin Exp Immunol. 1993 Nov;94(2):267-72.

PubMed [citation]

PMID:: 7900940
PMCID:: PMC1534221

Homozygous hereditary C1q deficiency and systemic lupus erythematosus. A new family and the molecular basis of C1q deficiency in three families.

Slingsby JH, Norsworthy P, Pearce G, Vaishnaw AK, Issler H, Morley BJ, Walport MJ.

Arthritis Rheum. 1996 Apr;39(4):663-70.

PubMed [citation]

PMID:: 8630118

See all PubMed Citations (6)

Details of each submission

From CeGaT Center for Human Genetics Tuebingen, SCV001371256.23

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002247271.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 34 of the C1QC protein (p.Gly34Arg). This variant is present in population databases (rs200206736, gnomAD 0.03%). This missense change has been observed in individual(s) with classical pathway complement deficiencies (PMID: 7900940, 8630118, 28082982, 30008451, 31357913). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is also known as p.Gly6Arg. ClinVar contains an entry for this variant (Variation ID: 17071). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic.

#	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: Oct 8, 2024

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