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NM_000312.4(PROC):c.91G>A (p.Glu31Lys) AND Thrombophilia due to protein C deficiency, autosomal dominant

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 28, 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:
RCV000226874.5

Allele description [Variation Report for NM_000312.4(PROC):c.91G>A (p.Glu31Lys)]

NM_000312.4(PROC):c.91G>A (p.Glu31Lys)

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.91G>A (p.Glu31Lys)
HGVS:
  • NC_000002.12:g.127421303G>A
  • NG_016323.1:g.7884G>A
  • NM_000312.4:c.91G>AMANE SELECT
  • NM_001375602.1:c.274G>A
  • NM_001375603.1:c.154G>A
  • NM_001375604.1:c.154G>A
  • NM_001375605.1:c.91G>A
  • NM_001375606.1:c.154G>A
  • NM_001375607.1:c.190-15G>A
  • NM_001375608.1:c.91G>A
  • NM_001375609.1:c.67G>A
  • NM_001375610.1:c.85G>A
  • NM_001375611.1:c.91G>A
  • NM_001375613.1:c.91G>A
  • NP_000303.1:p.Glu31Lys
  • NP_000303.1:p.Glu31Lys
  • NP_001362531.1:p.Glu92Lys
  • NP_001362532.1:p.Glu52Lys
  • NP_001362533.1:p.Glu52Lys
  • NP_001362534.1:p.Glu31Lys
  • NP_001362535.1:p.Glu52Lys
  • NP_001362537.1:p.Glu31Lys
  • NP_001362538.1:p.Glu23Lys
  • NP_001362539.1:p.Glu29Lys
  • NP_001362540.1:p.Glu31Lys
  • NP_001362542.1:p.Glu31Lys
  • LRG_599t1:c.91G>A
  • LRG_599:g.7884G>A
  • LRG_599p1:p.Glu31Lys
  • NC_000002.11:g.128178879G>A
  • NM_000312.3:c.91G>A
Protein change:
E23K
Links:
dbSNP: rs779710709
NCBI 1000 Genomes Browser:
rs779710709
Molecular consequence:
  • NM_001375607.1:c.190-15G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000312.4:c.91G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375602.1:c.274G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375603.1:c.154G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375604.1:c.154G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375605.1:c.91G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375606.1:c.154G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375608.1:c.91G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375609.1:c.67G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375610.1:c.85G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375611.1:c.91G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375613.1:c.91G>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
SCV000284569Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Aug 28, 2021) 		germlineclinical testing

PubMed (2)
[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

Hereditary protein C deficiency in Indian patients with venous thrombosis.

Pai N, Ghosh K, Shetty S.

Ann Hematol. 2012 Sep;91(9):1471-6. doi: 10.1007/s00277-012-1483-5. Epub 2012 May 11.

PubMed [citation]
PMID:
22576310

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 Invitae, SCV000284569.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces glutamic acid with lysine at codon 31 of the PROC protein (p.Glu31Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs779710709, ExAC 0.01%). This missense change has been observed in individual(s) with extrahepatic vein thrombosis and reduced protein C levels and activity (PMID: 22576310). 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: "Benign"; 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: Feb 7, 2023