NM_000821.7(GGCX):c.1595T>C (p.Ile532Thr) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 14, 2022
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:: RCV002634381.2

Allele description [Variation Report for NM_000821.7(GGCX):c.1595T>C (p.Ile532Thr)]

NM_000821.7(GGCX):c.1595T>C (p.Ile532Thr)

Gene:

GGCX:gamma-glutamyl carboxylase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p11.2

Genomic location:

Preferred name:

NM_000821.7(GGCX):c.1595T>C (p.Ile532Thr)

HGVS:

NC_000002.12:g.85551826A>G
NG_011811.2:g.14709T>C
NM_000821.7:c.1595T>CMANE SELECT
NM_001142269.4:c.1424T>C
NP_000812.2:p.Ile532Thr
NP_001135741.1:p.Ile475Thr
LRG_592t1:c.1595T>C
LRG_592:g.14709T>C
LRG_592p1:p.Ile532Thr
NC_000002.11:g.85778949A>G

Protein change:

I475T

Molecular consequence:

NM_000821.7:c.1595T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001142269.4:c.1424T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Hutchinson Gilford Progeria Syndrome cell line response to oncogenic challenge
Hutchinson Gilford Progeria Syndrome cell line response to oncogenic challenge
Accession: GDS5426

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003524698	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 14, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21435120, 33507293, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003524698

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 14, 2022)

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	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Novel phenotype and γ-glutamyl carboxylase mutations in combined deficiency of vitamin K-dependent coagulation factors.

Lunghi B, Redaelli R, Caimi TM, Corno AR, Bernardi F, Marchetti G.

Haemophilia. 2011 Sep;17(5):822-4. doi: 10.1111/j.1365-2516.2011.02524.x. Epub 2011 Mar 24. No abstract available.

PubMed [citation]

PMID:: 21435120

γ-Glutamyl carboxylase mutations differentially affect the biological function of vitamin K-dependent proteins.

Hao Z, Jin DY, Chen X, Schurgers LJ, Stafford DW, Tie JK.

Blood. 2021 Jan 28;137(4):533-543. doi: 10.1182/blood.2020006329.

PubMed [citation]

PMID:: 33507293
PMCID:: PMC7845004

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003524698.1

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

Description

This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 532 of the GGCX protein (p.Ile532Thr). This variant is present in population databases (rs375643655, gnomAD 0.008%). This missense change has been observed in individual(s) with deficiency of vitamin K-dependent clotting factors (PMID: 21435120). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects GGCX function (PMID: 33507293). 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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