NM_000249.4(MLH1):c.453+1G>T AND Lynch syndrome

Clinical significance:Likely pathogenic (Last evaluated: Jun 21, 2019)

Review status:3 stars out of maximum of 4 stars

reviewed by expert panel

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000075712.3

Allele description [Variation Report for NM_000249.4(MLH1):c.453+1G>T]

NM_000249.4(MLH1):c.453+1G>T

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.453+1G>T
HGVS:
  • NC_000003.12:g.37007064G>T
  • NG_007109.2:g.18715G>T
  • NM_000249.4:c.453+1G>TMANE SELECT
  • NM_001167617.3:c.159+1G>T
  • NM_001167618.3:c.-271+1G>T
  • NM_001167619.3:c.-179+1G>T
  • NM_001258271.2:c.453+1G>T
  • NM_001258273.2:c.-271+1G>T
  • NM_001258274.3:c.-271+1G>T
  • NM_001354615.2:c.-179+1G>T
  • NM_001354616.2:c.-179+1G>T
  • NM_001354617.2:c.-271+1G>T
  • NM_001354618.2:c.-271+1G>T
  • NM_001354619.2:c.-271+1G>T
  • NM_001354620.2:c.159+1G>T
  • NM_001354621.2:c.-364+1G>T
  • NM_001354622.2:c.-477+1G>T
  • NM_001354623.2:c.-477+1G>T
  • NM_001354624.2:c.-374+1G>T
  • NM_001354625.2:c.-282+1G>T
  • NM_001354626.2:c.-374+1G>T
  • NM_001354627.2:c.-374+1G>T
  • NM_001354628.2:c.453+1G>T
  • NM_001354629.2:c.354+1G>T
  • NM_001354630.2:c.453+1G>T
  • LRG_216t1:c.453+1G>T
  • LRG_216:g.18715G>T
  • NC_000003.11:g.37048555G>T
  • NM_000249.3:c.453+1G>T
Links:
dbSNP: rs267607750
NCBI 1000 Genomes Browser:
rs267607750
Molecular consequence:
  • NM_000249.4:c.453+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001167617.3:c.159+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001167618.3:c.-271+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001167619.3:c.-179+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001258271.2:c.453+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001258273.2:c.-271+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001258274.3:c.-271+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001354615.2:c.-179+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001354616.2:c.-179+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001354617.2:c.-271+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001354618.2:c.-271+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001354619.2:c.-271+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001354620.2:c.159+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001354621.2:c.-364+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001354622.2:c.-477+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001354623.2:c.-477+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001354624.2:c.-374+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001354625.2:c.-282+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001354626.2:c.-374+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001354627.2:c.-374+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001354628.2:c.453+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001354629.2:c.354+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001354630.2:c.453+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Lynch syndrome
Synonyms:
Familial nonpolyposis colon cancer
Identifiers:
MONDO: MONDO:0005835; MedGen: C4552100; OMIM: PS120435

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000106716International Society for Gastrointestinal Hereditary Tumours (InSiGHT)reviewed by expert panel
Likely pathogenic
(Jun 21, 2019)
germlinecuration

Citation Link,

SCV000592359Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR)criteria provided, single submitter
Pathogenic
(Oct 10, 2014)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing, curation

Citations

PubMed

Quantitative PCR high-resolution melting (qPCR-HRM) curve analysis, a new approach to simultaneously screen point mutations and large rearrangements: application to MLH1 germline mutations in Lynch syndrome.

Rouleau E, Lefol C, Bourdon V, Coulet F, Noguchi T, Soubrier F, Bi├Ęche I, Olschwang S, Sobol H, Lidereau R.

Hum Mutat. 2009 Jun;30(6):867-75. doi: 10.1002/humu.20947.

PubMed [citation]
PMID:
19224586

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From International Society for Gastrointestinal Hereditary Tumours (InSiGHT), SCV000106716.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

Interrupts canonical donor splice site

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

From Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV000592359.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

Support Center