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NM_000312.4(PROC):c.118C>T (p.Arg40Cys) AND Thrombophilia due to protein C deficiency, autosomal dominant

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 26, 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:
RCV001347080.4

Allele description [Variation Report for NM_000312.4(PROC):c.118C>T (p.Arg40Cys)]

NM_000312.4(PROC):c.118C>T (p.Arg40Cys)

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.118C>T (p.Arg40Cys)
HGVS:
  • NC_000002.12:g.127421330C>T
  • NG_016323.1:g.7911C>T
  • NM_000312.3:c.118C>T
  • NM_000312.4:c.118C>TMANE SELECT
  • NM_001375602.1:c.301C>T
  • NM_001375603.1:c.181C>T
  • NM_001375604.1:c.181C>T
  • NM_001375605.1:c.118C>T
  • NM_001375606.1:c.181C>T
  • NM_001375607.1:c.202C>T
  • NM_001375608.1:c.118C>T
  • NM_001375609.1:c.94C>T
  • NM_001375610.1:c.112C>T
  • NM_001375611.1:c.118C>T
  • NM_001375613.1:c.118C>T
  • NP_000303.1:p.Arg40Cys
  • NP_001362531.1:p.Arg101Cys
  • NP_001362532.1:p.Arg61Cys
  • NP_001362533.1:p.Arg61Cys
  • NP_001362534.1:p.Arg40Cys
  • NP_001362535.1:p.Arg61Cys
  • NP_001362536.1:p.Arg68Cys
  • NP_001362537.1:p.Arg40Cys
  • NP_001362538.1:p.Arg32Cys
  • NP_001362539.1:p.Arg38Cys
  • NP_001362540.1:p.Arg40Cys
  • NP_001362542.1:p.Arg40Cys
  • LRG_599t1:c.118C>T
  • LRG_599:g.7911C>T
  • NC_000002.11:g.128178906C>T
Protein change:
R101C
Links:
dbSNP: rs199514227
NCBI 1000 Genomes Browser:
rs199514227
Molecular consequence:
  • NM_000312.4:c.118C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375602.1:c.301C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375603.1:c.181C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375604.1:c.181C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375605.1:c.118C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375606.1:c.181C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375607.1:c.202C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375608.1:c.118C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375609.1:c.94C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375610.1:c.112C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375611.1:c.118C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375613.1:c.118C>T - 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
SCV001541324Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Sep 26, 2021) 		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

Scanning method to establish the molecular basis of protein C deficiencies.

Gandrille S, Goossens M, Aiach M.

Hum Mutat. 1994;4(1):20-30.

PubMed [citation]
PMID:
7951255

Identification of 58 Mutations (26 Novel) in 94 of 109 Symptomatic Spanish Probands with Protein C Deficiency.

Martos L, Fernández-Pardo Á, López-Fernández MF, Ibáñez F, Herrero S, Tàssies D, González-Porras JR, Solmoirago MJ, Costa MJ, Reverter JC, Marco P, Roldán V, Lecumberri R, Velasco F, Oto J, Iruin G, Alonso MN, Vayá A, Bonanad S, Ferrando F, Martí E, Cid AR, et al.

Thromb Haemost. 2019 Sep;119(9):1409-1418. doi: 10.1055/s-0039-1692440. Epub 2019 Jun 29.

PubMed [citation]
PMID:
31254973
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001541324.3

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

Description

This sequence change replaces arginine with cysteine at codon 40 of the PROC protein (p.Arg40Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs199514227, ExAC 0.003%). This missense change has been observed in individual(s) with protein C deficiency (PMID: 7951255, 31254973). This variant is also known as 1381C>T (-3Arg>Cys). ClinVar contains an entry for this variant (Variation ID: 1043032). 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.

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

Last Updated: Oct 13, 2024