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NM_000311.5(PRNP):c.625G>A (p.Val209Met) AND Huntington disease-like 1

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jan 12, 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:
RCV001913502.4

Allele description [Variation Report for NM_000311.5(PRNP):c.625G>A (p.Val209Met)]

NM_000311.5(PRNP):c.625G>A (p.Val209Met)

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.625G>A (p.Val209Met)
HGVS:
  • NC_000020.11:g.4699845G>A
  • NG_009087.1:g.18695G>A
  • NM_000311.5:c.625G>AMANE SELECT
  • NM_001080121.3:c.625G>A
  • NM_001080122.3:c.625G>A
  • NM_001080123.3:c.625G>A
  • NM_001271561.3:c.*314G>A
  • NM_183079.4:c.625G>A
  • NP_000302.1:p.Val209Met
  • NP_001073590.1:p.Val209Met
  • NP_001073591.1:p.Val209Met
  • NP_001073592.1:p.Val209Met
  • NP_898902.1:p.Val209Met
  • NC_000020.10:g.4680491G>A
Protein change:
V209M
Links:
dbSNP: rs758820257
NCBI 1000 Genomes Browser:
rs758820257
Molecular consequence:
  • NM_001271561.3:c.*314G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000311.5:c.625G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001080121.3:c.625G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001080122.3:c.625G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001080123.3:c.625G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_183079.4:c.625G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Huntington disease-like 1 (HDL1)
Synonyms:
HUNTINGTON-LIKE NEURODEGENERATIVE DISORDER 1; HUNTINGTON-LIKE NEURODEGENERATIVE DISORDER, AUTOSOMAL DOMINANT; PRION DISEASE, EARLY-ONSET, WITH PROMINENT PSYCHIATRIC FEATURES
Identifiers:
MONDO: MONDO:0011299; MedGen: C1864112; Orphanet: 157941; OMIM: 603218

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002181610Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jan 12, 2022) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Thermodynamic stabilization of the folded domain of prion protein inhibits prion infection in vivo.

Kong Q, Mills JL, Kundu B, Li X, Qing L, Surewicz K, Cali I, Huang S, Zheng M, Swietnicki W, Sönnichsen FD, Gambetti P, Surewicz WK.

Cell Rep. 2013 Jul 25;4(2):248-54. doi: 10.1016/j.celrep.2013.06.030. Epub 2013 Jul 18.

PubMed [citation]
PMID:
23871665
PMCID:
PMC3766954

PRNP allelic series from 19 years of prion protein gene sequencing at the MRC Prion Unit.

Beck JA, Poulter M, Campbell TA, Adamson G, Uphill JB, Guerreiro R, Jackson GS, Stevens JC, Manji H, Collinge J, Mead S.

Hum Mutat. 2010 Jul;31(7):E1551-63. doi: 10.1002/humu.21281.

PubMed [citation]
PMID:
20583301
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002181610.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

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. Experimental studies have shown that this missense change does not substantially affect PRNP function (PMID: 23871665). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This missense change has been observed in individual(s) with clinical features of PRNP-related conditions (PMID: 20583301). This variant is present in population databases (rs758820257, gnomAD 0.003%). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 209 of the PRNP protein (p.Val209Met).

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

Last Updated: Sep 29, 2024