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NM_000312.4(PROC):c.206C>T (p.Ala69Val) AND Thrombophilia due to protein C deficiency, autosomal dominant

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 16, 2019
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:
RCV001238309.6

Allele description [Variation Report for NM_000312.4(PROC):c.206C>T (p.Ala69Val)]

NM_000312.4(PROC):c.206C>T (p.Ala69Val)

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.206C>T (p.Ala69Val)
HGVS:
  • NC_000002.12:g.127421418C>T
  • NG_016323.1:g.7999C>T
  • NM_000312.4:c.206C>TMANE SELECT
  • NM_001375602.1:c.389C>T
  • NM_001375603.1:c.269C>T
  • NM_001375604.1:c.269C>T
  • NM_001375605.1:c.206C>T
  • NM_001375606.1:c.269C>T
  • NM_001375607.1:c.290C>T
  • NM_001375608.1:c.206C>T
  • NM_001375609.1:c.182C>T
  • NM_001375610.1:c.200C>T
  • NM_001375611.1:c.206C>T
  • NM_001375613.1:c.206C>T
  • NP_000303.1:p.Ala69Val
  • NP_001362531.1:p.Ala130Val
  • NP_001362532.1:p.Ala90Val
  • NP_001362533.1:p.Ala90Val
  • NP_001362534.1:p.Ala69Val
  • NP_001362535.1:p.Ala90Val
  • NP_001362536.1:p.Ala97Val
  • NP_001362537.1:p.Ala69Val
  • NP_001362538.1:p.Ala61Val
  • NP_001362539.1:p.Ala67Val
  • NP_001362540.1:p.Ala69Val
  • NP_001362542.1:p.Ala69Val
  • LRG_599t1:c.206C>T
  • LRG_599:g.7999C>T
  • NC_000002.11:g.128178994C>T
  • NM_000312.3:c.206C>T
Protein change:
A130V
Links:
dbSNP: rs984698204
NCBI 1000 Genomes Browser:
rs984698204
Molecular consequence:
  • NM_000312.4:c.206C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375602.1:c.389C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375603.1:c.269C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375604.1:c.269C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375605.1:c.206C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375606.1:c.269C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375607.1:c.290C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375608.1:c.206C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375609.1:c.182C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375610.1:c.200C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375611.1:c.206C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375613.1:c.206C>T - 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
SCV001411112Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Sep 16, 2019) 		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, SCV001411112.5

#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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with PROC-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with valine at codon 69 of the PROC protein (p.Ala69Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine.

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

Last Updated: Feb 20, 2024