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:: RCV000226874.6

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

Recent activity

Clear Turn Off Turn On

JGI_XZG20191.rev NIH_XGC_tropGas7 Xenopus tropicalis cDNA clone IMAGE:7535794 3'...
JGI_XZG20191.rev NIH_XGC_tropGas7 Xenopus tropicalis cDNA clone IMAGE:7535794 3', mRNA sequence
gi|57371848|gnl|dbEST|27098611|gb|C 50.1|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000284569	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 28, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22576310, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000284569

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 28, 2021)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000284569.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine