NM_002528.7(NTHL1):c.503T>C (p.Ile168Thr) AND Hereditary cancer-predisposing syndrome

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Jan 22, 2022
Review status:: criteria provided, conflicting classifications

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:: RCV001023853.9

Allele description [Variation Report for NM_002528.7(NTHL1):c.503T>C (p.Ile168Thr)]

NM_002528.7(NTHL1):c.503T>C (p.Ile168Thr)

Gene:

NTHL1:nth like DNA glycosylase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p13.3

Genomic location:

Preferred name:

NM_002528.7(NTHL1):c.503T>C (p.Ile168Thr)

HGVS:

NC_000016.10:g.2044652A>G
NG_005895.1:g.347A>G
NG_008412.1:g.8215T>C
NM_001318193.2:c.355-926T>C
NM_001318194.2:c.173T>C
NM_002528.7:c.503T>CMANE SELECT
NP_001305123.1:p.Ile58Thr
NP_002519.2:p.Ile168Thr
LRG_1366t1:c.503T>C
LRG_1366:g.8215T>C
LRG_1366p1:p.Ile168Thr
LRG_487:g.347A>G
NC_000016.9:g.2094653A>G
NM_002528.5:c.527T>C
NM_002528.6:c.527T>C

Protein change:

I168T

Links:

dbSNP: rs1805378

NCBI 1000 Genomes Browser:

rs1805378

Molecular consequence:

NM_001318193.2:c.355-926T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001318194.2:c.173T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_002528.7:c.503T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001185786	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Feb 18, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31227763, 31285513 Citation Link,
SCV002528982	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Uncertain significance (Jan 22, 2022)	germline	curation	PubMed (6) [See all records that cite these PMIDs] 31285513, 31227763, 32581083, 33454955, 23852950, 33980861 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001185786

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely benign
(Feb 18, 2020)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV002528982

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Uncertain significance
(Jan 22, 2022)

germline

curation

PubMed (6)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing, curation

Citations

PubMed

Contribution of New Adenomatous Polyposis Predisposition Genes in an Unexplained Attenuated Spanish Cohort by Multigene Panel Testing.

Lorca V, Rueda D, Martín-Morales L, Fernández-Aceñero MJ, Grolleman J, Poves C, Llovet P, Tapial S, García-Barberán V, Sanz J, Pérez-Segura P, de Voer RM, Díaz-Rubio E, de la Hoya M, Caldés T, Garre P.

Sci Rep. 2019 Jul 8;9(1):9814. doi: 10.1038/s41598-019-46403-5.

PubMed [citation]

PMID:: 31285513
PMCID:: PMC6614360

NTHL1 biallelic mutations seldom cause colorectal cancer, serrated polyposis or a multi-tumor phenotype, in absence of colorectal adenomas.

Belhadj S, Quintana I, Mur P, Munoz-Torres PM, Alonso MH, Navarro M, Terradas M, Piñol V, Brunet J, Moreno V, Lázaro C, Capellá G, Valle L.

Sci Rep. 2019 Jun 21;9(1):9020. doi: 10.1038/s41598-019-45281-1.

PubMed [citation]

PMID:: 31227763
PMCID:: PMC6588610

See all PubMed Citations (6)

Details of each submission

From Ambry Genetics, SCV001185786.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

#	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 Sema4, Sema4, SCV002528982.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (6)

#	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

Last Updated: May 19, 2024

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