NM_000311.5(PRNP):c.628G>A (p.Val210Ile) AND Inborn genetic diseases

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 29, 2024
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:
RCV004018625.1

Allele description [Variation Report for NM_000311.5(PRNP):c.628G>A (p.Val210Ile)]

NM_000311.5(PRNP):c.628G>A (p.Val210Ile)

Gene:
PRNP:prion protein (Kanno blood group) [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
20p13
Genomic location:
Preferred name:
NM_000311.5(PRNP):c.628G>A (p.Val210Ile)
Other names:
PRNP, VAL210ILE (rs74315407)
HGVS:
  • NC_000020.11:g.4699848G>A
  • NG_009087.1:g.18698G>A
  • NM_000311.5:c.628G>AMANE SELECT
  • NM_001080121.3:c.628G>A
  • NM_001080122.3:c.628G>A
  • NM_001080123.3:c.628G>A
  • NM_001271561.3:c.*317G>A
  • NM_183079.4:c.628G>A
  • NP_000302.1:p.Val210Ile
  • NP_001073590.1:p.Val210Ile
  • NP_001073591.1:p.Val210Ile
  • NP_001073592.1:p.Val210Ile
  • NP_898902.1:p.Val210Ile
  • NC_000020.10:g.4680494G>A
  • NM_000311.3:c.628G>A
  • P04156:p.Val210Ile
Protein change:
V210I; VAL210ILE
Links:
UniProtKB: P04156#VAR_006475; OMIM: 176640.0014; dbSNP: rs74315407
NCBI 1000 Genomes Browser:
rs74315407
Molecular consequence:
  • NM_001271561.3:c.*317G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000311.5:c.628G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001080121.3:c.628G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001080122.3:c.628G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001080123.3:c.628G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_183079.4:c.628G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Inborn genetic diseases
Identifiers:
MeSH: D030342; MedGen: C0950123

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
SCV005011763Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Jan 29, 2024) 		germlineclinical testing

PubMed (12)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

A new point mutation of the prion protein gene in Creutzfeldt-Jakob disease.

Pocchiari M, Salvatore M, Cutruzzolá F, Genuardi M, Allocatelli CT, Masullo C, Macchi G, Alemá G, Galgani S, Xi YG, et al.

Ann Neurol. 1993 Dec;34(6):802-7.

PubMed [citation]
PMID:
7902693

A Japanese case of Creutzfeldt-Jakob disease with a point mutation in the prion protein gene at codon 210.

Furukawa H, Kitamoto T, Hashiguchi H, Tateishi J.

J Neurol Sci. 1996 Sep 15;141(1-2):120-2.

PubMed [citation]
PMID:
8880705
See all PubMed Citations (12)

Details of each submission

From Ambry Genetics, SCV005011763.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (12)

Description

The c.628G>A (p.V210I) alteration is located in exon 2 (coding exon 1) of the PRNP gene. This alteration results from a G to A substitution at nucleotide position 628, causing the valine (V) at amino acid position 210 to be replaced by an isoleucine (I). Based on data from gnomAD, the A allele has an overall frequency of 0.001% (2/251460) total alleles studied. The highest observed frequency was 0.002% (2/113744) of European (non-Finnish) alleles. This variant was reported in multiple individuals who met clinical criteria for genetic prion disease (Mastrianni, 2001; Renard, 2018; Xiao, 2020), and multiple individuals with features consistent with genetic prion disease (Pocchiari, 1993; Mouillet-Richard, 1999; Furukawa, 1996; Mastrianni, 2001; Tajima, 2014; Conte, 2015; Imbriani, 2016; Xiao, 2020). This variant was also reported in unaffected family members suggesting reduced penetrance (Pocchiari, 1993; Mouillet-Richard, 1999). This amino acid position is well conserved in available vertebrate species. Based on internal structural analysis, p.V210I is moderately destabilizing to the local structure (van der Kamp, 2010; Jodoin, 2007). In multiple assays testing PRNP function, this variant showed functionally abnormal results (Peters, 2016; Jodoin, 2007). Based on the available evidence, this alteration is classified as pathogenic.

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

Last Updated: Sep 29, 2024