NM_000249.4(MLH1):c.452C>T (p.Thr151Met) AND not provided

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Aug 7, 2023
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:: RCV001569830.15

Allele description [Variation Report for NM_000249.4(MLH1):c.452C>T (p.Thr151Met)]

NM_000249.4(MLH1):c.452C>T (p.Thr151Met)

Gene:

MLH1:mutL homolog 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000249.4(MLH1):c.452C>T (p.Thr151Met)

HGVS:

NC_000003.12:g.37007062C>T
NG_007109.2:g.18713C>T
NM_000249.4:c.452C>TMANE SELECT
NM_001167617.3:c.158C>T
NM_001167618.3:c.-272C>T
NM_001167619.3:c.-180C>T
NM_001258271.2:c.452C>T
NM_001258273.2:c.-272C>T
NM_001258274.3:c.-272C>T
NM_001354615.2:c.-180C>T
NM_001354616.2:c.-180C>T
NM_001354617.2:c.-272C>T
NM_001354618.2:c.-272C>T
NM_001354619.2:c.-272C>T
NM_001354620.2:c.158C>T
NM_001354621.2:c.-365C>T
NM_001354622.2:c.-478C>T
NM_001354623.2:c.-478C>T
NM_001354624.2:c.-375C>T
NM_001354625.2:c.-283C>T
NM_001354626.2:c.-375C>T
NM_001354627.2:c.-375C>T
NM_001354628.2:c.452C>T
NM_001354629.2:c.353C>T
NM_001354630.2:c.452C>T
NP_000240.1:p.Thr151Met
NP_000240.1:p.Thr151Met
NP_001161089.1:p.Thr53Met
NP_001245200.1:p.Thr151Met
NP_001341549.1:p.Thr53Met
NP_001341557.1:p.Thr151Met
NP_001341558.1:p.Thr118Met
NP_001341559.1:p.Thr151Met
LRG_216t1:c.452C>T
LRG_216:g.18713C>T
LRG_216p1:p.Thr151Met
NC_000003.11:g.37048553C>T
NM_000249.3:c.452C>T
p.T151M

Protein change:

T118M

Links:

dbSNP: rs776969475

NCBI 1000 Genomes Browser:

rs776969475

Molecular consequence:

NM_001167618.3:c.-272C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167619.3:c.-180C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258273.2:c.-272C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258274.3:c.-272C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354615.2:c.-180C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354616.2:c.-180C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354617.2:c.-272C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354618.2:c.-272C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354619.2:c.-272C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354621.2:c.-365C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354622.2:c.-478C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354623.2:c.-478C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354624.2:c.-375C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354625.2:c.-283C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354626.2:c.-375C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354627.2:c.-375C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000249.4:c.452C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001167617.3:c.158C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001258271.2:c.452C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354620.2:c.158C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354628.2:c.452C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354629.2:c.353C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354630.2:c.452C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

uncharacterized protein LOC111802315 isoform X2 [Cucurbita pepo subsp. pepo]
uncharacterized protein LOC111802315 isoform X2 [Cucurbita pepo subsp. pepo]
gi|1333135298|ref|XP_023542399.1|

Protein

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
SCV001793986	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Aug 7, 2023)	germline	clinical testing	Citation Link,
SCV004149360	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Uncertain significance (Jun 1, 2023)	germline	clinical testing	Citation Link,
SCV004220889	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Nov 9, 2022)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 33471991, 32658311, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001793986

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Aug 7, 2023)

germline

clinical testing

Citation Link,

SCV004149360

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Uncertain significance
(Jun 1, 2023)

germline

clinical testing

Citation Link,

SCV004220889

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Nov 9, 2022)

unknown

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women.

Breast Cancer Association Consortium., Dorling L, Carvalho S, Allen J, González-Neira A, Luccarini C, Wahlström C, Pooley KA, Parsons MT, Fortuno C, Wang Q, Bolla MK, Dennis J, Keeman R, Alonso MR, Álvarez N, Herraez B, Fernandez V, Núñez-Torres R, Osorio A, Valcich J, Li M, et al.

N Engl J Med. 2021 Feb 4;384(5):428-439. doi: 10.1056/NEJMoa1913948. Epub 2021 Jan 20.

PubMed [citation]

PMID:: 33471991
PMCID:: PMC7611105

Germline pathogenic variant spectrum in 25 cancer susceptibility genes in Turkish breast and colorectal cancer patients and elderly controls.

Akcay IM, Celik E, Agaoglu NB, Alkurt G, Kizilboga Akgun T, Yildiz J, Enc F, Kir G, Canbek S, Kilic A, Zemheri E, Ezberci F, Ozcelik M, Dinler Doganay G, Doganay L.

Int J Cancer. 2021 Jan 15;148(2):285-295. doi: 10.1002/ijc.33199. Epub 2020 Aug 19.

PubMed [citation]

PMID:: 32658311

See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV001793986.2

#	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 significant frequency in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 22753075, 30122538)

#	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

From CeGaT Center for Human Genetics Tuebingen, SCV004149360.9

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

#	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		1	not provided	not provided	not provided

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV004220889.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The frequency of this variant in the general population, 0.000087 (3/34588 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in individuals with breast cancer (PMID: 33471991 (2021) and colorectal cancer (PMID: 32658311 (2021)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.

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

Last Updated: Oct 8, 2024

ClinVar

Relating variation to medicine