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NM_000312.4(PROC):c.1268del (p.Gly423fs) AND Thrombophilia due to protein C deficiency, autosomal dominant

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 15, 1996
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV000000705.3

Allele description [Variation Report for NM_000312.4(PROC):c.1268del (p.Gly423fs)]

NM_000312.4(PROC):c.1268del (p.Gly423fs)

Gene:
PROC:protein C, inactivator of coagulation factors Va and VIIIa [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
2q14.3
Genomic location:
Preferred name:
NM_000312.4(PROC):c.1268del (p.Gly423fs)
HGVS:
  • NC_000002.12:g.127428828del
  • NG_016323.1:g.15409del
  • NM_000312.4:c.1268delMANE SELECT
  • NM_001375602.1:c.1451del
  • NM_001375603.1:c.1433del
  • NM_001375604.1:c.1331del
  • NM_001375605.1:c.1370del
  • NM_001375606.1:c.1436del
  • NM_001375607.1:c.1454del
  • NM_001375608.1:c.1211del
  • NM_001375609.1:c.1244del
  • NM_001375610.1:c.1262del
  • NM_001375611.1:c.1268del
  • NM_001375613.1:c.1268del
  • NP_000303.1:p.Gly423Valfs
  • NP_000303.1:p.Gly423fs
  • NP_001362531.1:p.Gly484fs
  • NP_001362532.1:p.Gly478fs
  • NP_001362533.1:p.Gly444fs
  • NP_001362534.1:p.Gly457fs
  • NP_001362535.1:p.Gly479fs
  • NP_001362536.1:p.Gly485fs
  • NP_001362537.1:p.Gly404fs
  • NP_001362538.1:p.Gly415fs
  • NP_001362539.1:p.Gly421fs
  • NP_001362540.1:p.Gly423fs
  • NP_001362542.1:p.Gly423fs
  • LRG_599t1:c.1268del
  • LRG_599:g.15409del
  • NC_000002.11:g.128186404del
  • NM_000312.3:c.1268del
  • NM_000312.3:c.1268delG
Note:
NCBI staff provided HGVS expressions for allelic variant 612283.0015 based on the sequence reported in Figure 3 of the paper by Yamamoto et al., 1992 (PubMed 1469096).
Protein change:
G404fs
Links:
OMIM: 612283.0015
Molecular consequence:
  • NM_000312.4:c.1268del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001375602.1:c.1451del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001375603.1:c.1433del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001375604.1:c.1331del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001375605.1:c.1370del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001375606.1:c.1436del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001375607.1:c.1454del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001375608.1:c.1211del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001375609.1:c.1244del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001375610.1:c.1262del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001375611.1:c.1268del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001375613.1:c.1268del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Thrombophilia due to protein C deficiency, autosomal dominant
Synonyms:
PROC DEFICIENCY, AUTOSOMAL DOMINANT; PROTEIN C DEFICIENCY, AUTOSOMAL DOMINANT; Thrombophilia, hereditary, due to protein C deficiency, autosomal dominant
Identifiers:
MONDO: MONDO:0008316; MedGen: C2674321; Orphanet: 745; OMIM: 176860

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000020855OMIM
no assertion criteria provided
Pathogenic
(May 15, 1996) 		germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Impaired secretion of the elongated mutant of protein C (protein C-Nagoya). Molecular and cellular basis for hereditary protein C deficiency.

Yamamoto K, Tanimoto M, Emi N, Matsushita T, Takamatsu J, Saito H.

J Clin Invest. 1992 Dec;90(6):2439-46.

PubMed [citation]
PMID:
1469096
PMCID:
PMC443400

Protein C Nagoya, an elongated mutant of protein C, is retained within the endoplasmic reticulum and is associated with GRP78 and GRP94.

Katsumi A, Senda T, Yamashita Y, Yamazaki T, Hamaguchi M, Kojima T, Kobayashi S, Saito H.

Blood. 1996 May 15;87(10):4164-75.

PubMed [citation]
PMID:
8639775

Details of each submission

From OMIM, SCV000020855.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In a 46-year-old Japanese man who had recurrent episodes of deep vein thrombosis and pulmonary embolism (THPH3; 176860), Yamamoto et al. (1992) identified a heterozygous 1-bp deletion, 8857delG, among 4 consecutive guanine nucleotides at codons 380 (TGG-trp) and 381 (GGT-gly) in exon 9 of the PROC gene, which encodes the C-terminal region. The deletion resulted in a frameshift and the substitution of the last 39 amino acids, gly381 to pro419, with 81 abnormal amino acid residues. The elongated variant was designated 'protein C Nagoya.' By transfection of COS-7 and other cells with an expression plasmid containing this mutation, the authors demonstrated that most of the mutant protein was retained within the cells where it undergoes degradation.

To determine the subcellular localization of protein C Nagoya, Katsumi et al. (1996) expressed the recombinant protein C bearing this mutation in Chinese hamster ovary (CHO) cells. The mutant protein C was not secreted from the cells. Immunoelectron microscopy indicated that protein C Nagoya was retained in the endoplasmic reticulum (ER), whereas wildtype protein C was observed in both the ER and Golgi apparatus. Metabolic radiolabeling with (35S) methionine in combination with chemical cross-linking showed that protein C Nagoya existed in the ER as a complex with 78-kD glucose-regulated protein (GRP78; 138120) and 94-kD glucose-regulated protein (GRP94; 191175). Because both GRP78 and GRP94 associate to a far lesser degree with wildtype protein C and with protein C Nagoya, the data suggested that both stress proteins function as molecular chaperones and work in concert with the folding and assembly of protein C.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 13, 2022