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NM_000312.4(PROC):c.151C>T (p.Arg51Cys) AND not provided

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 11, 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:
RCV002222311.1

Allele description [Variation Report for NM_000312.4(PROC):c.151C>T (p.Arg51Cys)]

NM_000312.4(PROC):c.151C>T (p.Arg51Cys)

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.151C>T (p.Arg51Cys)
HGVS:
  • NC_000002.12:g.127421363C>T
  • NG_016323.1:g.7944C>T
  • NM_000312.4:c.151C>TMANE SELECT
  • NM_001375602.1:c.334C>T
  • NM_001375603.1:c.214C>T
  • NM_001375604.1:c.214C>T
  • NM_001375605.1:c.151C>T
  • NM_001375606.1:c.214C>T
  • NM_001375607.1:c.235C>T
  • NM_001375608.1:c.151C>T
  • NM_001375609.1:c.127C>T
  • NM_001375610.1:c.145C>T
  • NM_001375611.1:c.151C>T
  • NM_001375613.1:c.151C>T
  • NP_000303.1:p.Arg51Cys
  • NP_001362531.1:p.Arg112Cys
  • NP_001362532.1:p.Arg72Cys
  • NP_001362533.1:p.Arg72Cys
  • NP_001362534.1:p.Arg51Cys
  • NP_001362535.1:p.Arg72Cys
  • NP_001362536.1:p.Arg79Cys
  • NP_001362537.1:p.Arg51Cys
  • NP_001362538.1:p.Arg43Cys
  • NP_001362539.1:p.Arg49Cys
  • NP_001362540.1:p.Arg51Cys
  • NP_001362542.1:p.Arg51Cys
  • LRG_599t1:c.151C>T
  • LRG_599:g.7944C>T
  • NC_000002.11:g.128178939C>T
  • NM_000312.3:c.151C>T
Protein change:
R112C
Links:
dbSNP: rs764546127
NCBI 1000 Genomes Browser:
rs764546127
Molecular consequence:
  • NM_000312.4:c.151C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375602.1:c.334C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375603.1:c.214C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375604.1:c.214C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375605.1:c.151C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375606.1:c.214C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375607.1:c.235C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375608.1:c.151C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375609.1:c.127C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375610.1:c.145C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375611.1:c.151C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375613.1:c.151C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002499733MVZ Dr. Eberhard & Partner Dortmund
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Jan 11, 2022) 		unknownclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From MVZ Dr. Eberhard & Partner Dortmund, SCV002499733.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

The patient shows reduced Protein C clotting (50% [67-122 %]).

Description

This sequence change from C to T causees an amino acid change from Arginine to Cysteine at position 51. The affected amino acid is therefore present in a functional domain called Gamma-carboxygluatmic acid-rich (GLA) domain. The variant is present in very low frequency in controls (Exome Sequencing Project, 1000 Genomes Project, and Exome Aggregation Consortium). It is listed in the mutation database HGMD (CM950976) as disease causing, as well as the missense change at the same amino acid residue R51H is listed as pathogenic (HGMD: CM000420). Multiple literature sources associate this variant with PROC deficiency and show an increased frequency in patients affected by deficiency (PMIDs: 7482420, 10669160, 32717757). Wu et al. (PMID: 24051141) determined significantly reduced protein levels in HeLa cells with this variant and discusses possible effects on biological activity caused by presence of this variant in the functional domain. In conclusion, this variant was determined to be pathogenic according to ACMG Guidelines.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknown1not providednot provided1not providednot providednot provided

Last Updated: Dec 24, 2023