NM_000821.7(GGCX):c.1492C>T (p.Arg498Cys) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 30, 2021
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:: RCV001861157.5

Allele description [Variation Report for NM_000821.7(GGCX):c.1492C>T (p.Arg498Cys)]

NM_000821.7(GGCX):c.1492C>T (p.Arg498Cys)

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.1492C>T (p.Arg498Cys)

HGVS:

NC_000002.12:g.85551929G>A
NG_011811.2:g.14606C>T
NM_000821.7:c.1492C>TMANE SELECT
NM_001142269.4:c.1321C>T
NP_000812.2:p.Arg498Cys
NP_001135741.1:p.Arg441Cys
LRG_592t1:c.1492C>T
LRG_592:g.14606C>T
LRG_592p1:p.Arg498Cys
NC_000002.11:g.85779052G>A
NM_000821.5:c.1492C>T

Protein change:

R441C

Links:

dbSNP: rs372161185

NCBI 1000 Genomes Browser:

rs372161185

Molecular consequence:

NM_000821.7:c.1492C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001142269.4:c.1321C>T - 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
SCV002287838	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 30, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25264593, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002287838

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 30, 2021)

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

Efficiency of exome sequencing for the molecular diagnosis of pseudoxanthoma elasticum.

Hosen MJ, Van Nieuwerburgh F, Steyaert W, Deforce D, Martin L, Leftheriotis G, De Paepe A, Coucke PJ, Vanakker OM.

J Invest Dermatol. 2015 Apr;135(4):992-998. doi: 10.1038/jid.2014.421. Epub 2014 Sep 29.

PubMed [citation]

PMID:: 25264593
PMCID:: PMC4378258

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, SCV002287838.2

#	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 arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 498 of the GGCX protein (p.Arg498Cys). This variant is present in population databases (rs372161185, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of pseudoxanthoma elasticum (PMID: 25264593). ClinVar contains an entry for this variant (Variation ID: 337264). 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 C15"). 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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