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NM_000312.4(PROC):c.1216A>G (p.Met406Val) AND not provided

Germline classification:
Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:
Nov 1, 2018
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000657992.22

Allele description [Variation Report for NM_000312.4(PROC):c.1216A>G (p.Met406Val)]

NM_000312.4(PROC):c.1216A>G (p.Met406Val)

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.1216A>G (p.Met406Val)
HGVS:
  • NC_000002.12:g.127428776A>G
  • NG_016323.1:g.15357A>G
  • NM_000312.4:c.1216A>GMANE SELECT
  • NM_001375602.1:c.1399A>G
  • NM_001375603.1:c.1381A>G
  • NM_001375604.1:c.1279A>G
  • NM_001375605.1:c.1318A>G
  • NM_001375606.1:c.1384A>G
  • NM_001375607.1:c.1402A>G
  • NM_001375608.1:c.1159A>G
  • NM_001375609.1:c.1192A>G
  • NM_001375610.1:c.1210A>G
  • NM_001375611.1:c.1216A>G
  • NM_001375613.1:c.1216A>G
  • NP_000303.1:p.Met406Val
  • NP_000303.1:p.Met406Val
  • NP_001362531.1:p.Met467Val
  • NP_001362532.1:p.Met461Val
  • NP_001362533.1:p.Met427Val
  • NP_001362534.1:p.Met440Val
  • NP_001362535.1:p.Met462Val
  • NP_001362536.1:p.Met468Val
  • NP_001362537.1:p.Met387Val
  • NP_001362538.1:p.Met398Val
  • NP_001362539.1:p.Met404Val
  • NP_001362540.1:p.Met406Val
  • NP_001362542.1:p.Met406Val
  • LRG_599t1:c.1216A>G
  • LRG_599:g.15357A>G
  • LRG_599p1:p.Met406Val
  • NC_000002.11:g.128186352A>G
  • NM_000312.3:c.1216A>G
Protein change:
M387V
Links:
dbSNP: rs1553425459
NCBI 1000 Genomes Browser:
rs1553425459
Molecular consequence:
  • NM_000312.4:c.1216A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375602.1:c.1399A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375603.1:c.1381A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375604.1:c.1279A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375605.1:c.1318A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375606.1:c.1384A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375607.1:c.1402A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375608.1:c.1159A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375609.1:c.1192A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375610.1:c.1210A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375611.1:c.1216A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375613.1:c.1216A>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
2

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000779763GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Likely pathogenic
(May 15, 2018) 		germlineclinical testing

Citation Link,

SCV000892579CeGaT Center for Human Genetics Tuebingen
criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)		Pathogenic
(Nov 1, 2018) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes2not providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000779763.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The M406V variant in the PROC gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. However, a missense variant at this same codon (M406I) as well as missense variants in neighboring codons (D401N, G403R, G404E, P405A, V407A, F410S) have been reported in the Human Gene Mutation Database in association with protein C deficiency (Kim et al., 2014; Inoue et al., 2017; Stenson et al., 2014). The M406V variant is not observed in large population cohorts (Lek et al., 2016). The M406V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret M406V as a likely pathogenic variant.

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

From CeGaT Center for Human Genetics Tuebingen, SCV000892579.25

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided2not providednot providednot provided

Last Updated: Jul 15, 2024