U.S. flag

An official website of the United States government

NM_000312.4(PROC):c.1195G>A (p.Glu399Lys) AND Thrombophilia due to protein C deficiency, autosomal dominant

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 31, 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:
RCV001909695.5

Allele description

NM_000312.4(PROC):c.1195G>A (p.Glu399Lys)

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.1195G>A (p.Glu399Lys)
HGVS:
  • NC_000002.12:g.127428755G>A
  • NG_016323.1:g.15336G>A
  • NM_000312.4:c.1195G>AMANE SELECT
  • NM_001375602.1:c.1378G>A
  • NM_001375603.1:c.1360G>A
  • NM_001375604.1:c.1258G>A
  • NM_001375605.1:c.1297G>A
  • NM_001375606.1:c.1363G>A
  • NM_001375607.1:c.1381G>A
  • NM_001375608.1:c.1138G>A
  • NM_001375609.1:c.1171G>A
  • NM_001375610.1:c.1189G>A
  • NM_001375611.1:c.1195G>A
  • NM_001375613.1:c.1195G>A
  • NP_000303.1:p.Glu399Lys
  • NP_001362531.1:p.Glu460Lys
  • NP_001362532.1:p.Glu454Lys
  • NP_001362533.1:p.Glu420Lys
  • NP_001362534.1:p.Glu433Lys
  • NP_001362535.1:p.Glu455Lys
  • NP_001362536.1:p.Glu461Lys
  • NP_001362537.1:p.Glu380Lys
  • NP_001362538.1:p.Glu391Lys
  • NP_001362539.1:p.Glu397Lys
  • NP_001362540.1:p.Glu399Lys
  • NP_001362542.1:p.Glu399Lys
  • LRG_599:g.15336G>A
  • NC_000002.11:g.128186331G>A
Protein change:
E380K
Links:
dbSNP: rs764239787
NCBI 1000 Genomes Browser:
rs764239787
Molecular consequence:
  • NM_000312.4:c.1195G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375602.1:c.1378G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375603.1:c.1360G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375604.1:c.1258G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375605.1:c.1297G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375606.1:c.1363G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375607.1:c.1381G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375608.1:c.1138G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375609.1:c.1171G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375610.1:c.1189G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375611.1:c.1195G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375613.1:c.1195G>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

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002183327Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Aug 31, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

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, SCV002183327.3

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 1409195). This variant has not been reported in the literature in individuals affected with PROC-related conditions. This variant is present in population databases (rs764239787, gnomAD 0.008%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 399 of the PROC protein (p.Glu399Lys).

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

Last Updated: Feb 20, 2024