NM_000391.4(TPP1):c.1192C>T (p.Leu398Phe) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 26, 2020
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:: RCV001298323.13

Allele description [Variation Report for NM_000391.4(TPP1):c.1192C>T (p.Leu398Phe)]

NM_000391.4(TPP1):c.1192C>T (p.Leu398Phe)

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.1192C>T (p.Leu398Phe)

HGVS:

NC_000011.10:g.6615516G>A
NG_008653.1:g.8946C>T
NM_000391.4:c.1192C>TMANE SELECT
NP_000382.3:p.Leu398Phe
LRG_830t1:c.1192C>T
LRG_830:g.8946C>T
LRG_830p1:p.Leu398Phe
NC_000011.9:g.6636747G>A
NM_000391.3:c.1192C>T

Protein change:

L398F

Links:

dbSNP: rs149319579

NCBI 1000 Genomes Browser:

rs149319579

Molecular consequence:

NM_000391.4:c.1192C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001487371	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 26, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001826246	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Jun 25, 2019)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001487371

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 26, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001826246

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Jun 25, 2019)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001487371.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces leucine with phenylalanine at codon 398 of the TPP1 protein (p.Leu398Phe). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is present in population databases (rs149319579, ExAC 0.008%). This variant has not been reported in the literature in individuals with TPP1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneDx, SCV001826246.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 10, 2024

ClinVar

Relating variation to medicine