NM_000312.4(PROC):c.1110C>A (p.His370Gln) AND Thrombophilia due to protein C deficiency, autosomal dominant

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 23, 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:: RCV001307199.6

Allele description [Variation Report for NM_000312.4(PROC):c.1110C>A (p.His370Gln)]

NM_000312.4(PROC):c.1110C>A (p.His370Gln)

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.1110C>A (p.His370Gln)

HGVS:

NC_000002.12:g.127428670C>A
NG_016323.1:g.15251C>A
NM_000312.4:c.1110C>AMANE SELECT
NM_001375602.1:c.1293C>A
NM_001375603.1:c.1275C>A
NM_001375604.1:c.1173C>A
NM_001375605.1:c.1212C>A
NM_001375606.1:c.1278C>A
NM_001375607.1:c.1296C>A
NM_001375608.1:c.1053C>A
NM_001375609.1:c.1086C>A
NM_001375610.1:c.1104C>A
NM_001375611.1:c.1110C>A
NM_001375613.1:c.1110C>A
NP_000303.1:p.His370Gln
NP_001362531.1:p.His431Gln
NP_001362532.1:p.His425Gln
NP_001362533.1:p.His391Gln
NP_001362534.1:p.His404Gln
NP_001362535.1:p.His426Gln
NP_001362536.1:p.His432Gln
NP_001362537.1:p.His351Gln
NP_001362538.1:p.His362Gln
NP_001362539.1:p.His368Gln
NP_001362540.1:p.His370Gln
NP_001362542.1:p.His370Gln
LRG_599:g.15251C>A
NC_000002.11:g.128186246C>A

Protein change:

H351Q

Links:

dbSNP: rs778063605

NCBI 1000 Genomes Browser:

rs778063605

Molecular consequence:

NM_000312.4:c.1110C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375602.1:c.1293C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375603.1:c.1275C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375604.1:c.1173C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375605.1:c.1212C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375606.1:c.1278C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375607.1:c.1296C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375608.1:c.1053C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375609.1:c.1086C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375610.1:c.1104C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375611.1:c.1110C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001375613.1:c.1110C>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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001496598	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 23, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22353194, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001496598

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 23, 2022)

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

Identification of genetic risk variants for deep vein thrombosis by multiplexed next-generation sequencing of 186 hemostatic/pro-inflammatory genes.

Lotta LA, Wang M, Yu J, Martinelli I, Yu F, Passamonti SM, Consonni D, Pappalardo E, Menegatti M, Scherer SE, Lewis LL, Akbar H, Wu Y, Bainbridge MN, Muzny DM, Mannucci PM, Gibbs RA, Peyvandi F.

BMC Med Genomics. 2012 Feb 21;5:7. doi: 10.1186/1755-8794-5-7.

PubMed [citation]

PMID:: 22353194
PMCID:: PMC3305575

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, SCV001496598.3

#	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 histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 370 of the PROC protein (p.His370Gln). This variant is present in population databases (rs778063605, gnomAD 0.006%). This missense change has been observed in individual(s) with deep vein thrombosis (PMID: 22353194). ClinVar contains an entry for this variant (Variation ID: 1009680). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PROC protein function. 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

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