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NM_000391.4(TPP1):c.1266G>C (p.Gln422His) AND Inborn genetic diseases

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 26, 2013
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:
RCV000210643.5

Allele description [Variation Report for NM_000391.4(TPP1):c.1266G>C (p.Gln422His)]

NM_000391.4(TPP1):c.1266G>C (p.Gln422His)

Gene:
TPP1:tripeptidyl peptidase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11p15.4
Genomic location:
Preferred name:
NM_000391.4(TPP1):c.1266G>C (p.Gln422His)
Other names:
5271G>C; p.Q422H:CAG>CAC
HGVS:
  • NC_000011.10:g.6615442C>G
  • NG_008653.1:g.9020G>C
  • NM_000391.4:c.1266G>CMANE SELECT
  • NP_000382.3:p.Gln422His
  • LRG_830t1:c.1266G>C
  • LRG_830:g.9020G>C
  • LRG_830p1:p.Gln422His
  • NC_000011.9:g.6636673C>G
  • NM_000391.3:c.1266G>C
  • O14773:p.Gln422His
Protein change:
Q422H
Links:
UniProtKB: O14773#VAR_009610; UniProtKB/Swiss-Prot: VAR_009610; dbSNP: rs121908200
NCBI 1000 Genomes Browser:
rs121908200
Molecular consequence:
  • NM_000391.4:c.1266G>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000262861Ambry Genetics
criteria provided, single submitter

(Ambry Autosomal Dominant and X-Linked criteria (10/2015))		Pathogenic
(Jun 26, 2013) 		germlineclinical testing

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Details of each submission

From Ambry Genetics, SCV000262861.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

​B1) TPP1 c.1266G>C (p.Q422H)The c.1266G>C (p.Q422H) alteration is located in exon 10 of the TPP1 gene. This alteration results from a G to C substitution at nucleotide position 1266, resulting in an amino acid substitution of glutamine (Q) for histidine (H) at codon 422.<u>​The missense change is rare in healthy cohorts</u>:Based on data from the NHLBI Exome Sequencing Project (ESP), the TPP1 c.1266G>C (p.Q422H) alteration has an overall frequency of approximately 0.01% (1/10758 total alleles studied). The C-allele was observed in 0.01% (1/7020) of European American alleles and has not been observed (0%) in African Americans among of 3738 total alleles studied. The alteration has not been observed in the homozygous state out of 5379 individuals. Allele frequency data for alterations at this nucleotide position are not currently available from the 1000 Genomes Project.<u>The altered amino acid is conserved throughout evolution</u>:The Q422 amino acid is conserved throughout vertebrate evolution.<u>The alteration is predicted deleterious by in silico models:</u>The Q422H alteration is predicted to be probably damaging by Polyphen and deleterious by SIFT in silico analyses.<u>The amino acid change has been observed in affected individuals:</u>This alteration is reported in the HGMD database (Accession# CM990373). This alteration is among the most common TPP1 mutations, accounting for ~7% of mutant alleles observed in affected individuals (Sleat, 1999).Based on the available evidence, the TPP1 c.1266G>C (p.Q422H) alteration is classified as a pathogenic mutation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Sep 29, 2024