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NM_000312.4(PROC):c.1000G>A (p.Gly334Ser) AND Thrombophilia due to protein C deficiency, autosomal dominant

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 29, 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:
RCV000195879.8

Allele description [Variation Report for NM_000312.4(PROC):c.1000G>A (p.Gly334Ser)]

NM_000312.4(PROC):c.1000G>A (p.Gly334Ser)

Gene:
PROC:protein C, inactivator of coagulation factors Va and VIIIa [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q14.3
Genomic location:
Preferred name:
NM_000312.4(PROC):c.1000G>A (p.Gly334Ser)
Other names:
G292S
HGVS:
  • NC_000002.12:g.127428560G>A
  • NG_016323.1:g.15141G>A
  • NM_000312.4:c.1000G>AMANE SELECT
  • NM_001375602.1:c.1183G>A
  • NM_001375603.1:c.1165G>A
  • NM_001375604.1:c.1063G>A
  • NM_001375605.1:c.1102G>A
  • NM_001375606.1:c.1168G>A
  • NM_001375607.1:c.1186G>A
  • NM_001375608.1:c.943G>A
  • NM_001375609.1:c.976G>A
  • NM_001375610.1:c.994G>A
  • NM_001375611.1:c.1000G>A
  • NM_001375613.1:c.1000G>A
  • NP_000303.1:p.Gly334Ser
  • NP_000303.1:p.Gly334Ser
  • NP_001362531.1:p.Gly395Ser
  • NP_001362532.1:p.Gly389Ser
  • NP_001362533.1:p.Gly355Ser
  • NP_001362534.1:p.Gly368Ser
  • NP_001362535.1:p.Gly390Ser
  • NP_001362536.1:p.Gly396Ser
  • NP_001362537.1:p.Gly315Ser
  • NP_001362538.1:p.Gly326Ser
  • NP_001362539.1:p.Gly332Ser
  • NP_001362540.1:p.Gly334Ser
  • NP_001362542.1:p.Gly334Ser
  • LRG_599t1:c.1000G>A
  • LRG_599:g.15141G>A
  • LRG_599p1:p.Gly334Ser
  • NC_000002.11:g.128186136G>A
  • NM_000312.3:c.1000G>A
  • P04070:p.Gly334Ser
Protein change:
G315S; GLY292SER
Links:
UniProtKB: P04070#VAR_006691; OMIM: 612283.0011; dbSNP: rs121918150
NCBI 1000 Genomes Browser:
rs121918150
Molecular consequence:
  • NM_000312.4:c.1000G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375602.1:c.1183G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375603.1:c.1165G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375604.1:c.1063G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375605.1:c.1102G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375606.1:c.1168G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375607.1:c.1186G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375608.1:c.943G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375609.1:c.976G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375610.1:c.994G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375611.1:c.1000G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375613.1:c.1000G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000253833Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Oct 29, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

The spectrum of genetic defects in a panel of 40 Dutch families with symptomatic protein C deficiency type I: heterogeneity and founder effects.

Reitsma PH, Poort SR, Allaart CF, Briët E, Bertina RM.

Blood. 1991 Aug 15;78(4):890-4.

PubMed [citation]
PMID:
1868249

Homozygous protein C deficiency: identification of a novel missense mutation that causes impaired secretion of the mutant protein C.

Yamamoto K, Matsushita T, Sugiura I, Takamatsu J, Iwasaki E, Wada H, Deguchi K, Shirakawa S, Saito H.

J Lab Clin Med. 1992 Jun;119(6):682-9.

PubMed [citation]
PMID:
1593215
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000253833.8

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 334 of the PROC protein (p.Gly334Ser). This variant is present in population databases (rs121918150, gnomAD 0.007%). This missense change has been observed in individuals with protein C deficiency (PMID: 1593215, 1868249). It has also been observed to segregate with disease in related individuals. This variant is also known as Gly292Ser. ClinVar contains an entry for this variant (Variation ID: 666). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PROC protein function. Experimental studies have shown that this missense change affects PROC function (PMID: 1593215). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Oct 13, 2024