NM_000249.4(MLH1):c.174_175delinsT (p.Leu58fs) AND Lynch syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 20, 2017
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:: RCV000586133.1

Allele description [Variation Report for NM_000249.4(MLH1):c.174_175delinsT (p.Leu58fs)]

NM_000249.4(MLH1):c.174_175delinsT (p.Leu58fs)

Gene:

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

Variant type:

Indel

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000249.4(MLH1):c.174_175delinsT (p.Leu58fs)

HGVS:

NC_000003.12:g.36996676_36996677delinsT
NG_007109.2:g.8327_8328delinsT
NG_008418.1:g.1628_1629delinsA
NM_000249.4:c.174_175delinsTMANE SELECT
NM_001167617.3:c.-116_-115delinsT
NM_001167618.3:c.-550_-549delinsT
NM_001167619.3:c.-458_-457delinsT
NM_001258271.2:c.174_175delinsT
NM_001258273.2:c.-517+3013_-517+3014delinsT
NM_001258274.3:c.-695_-694delinsT
NM_001354615.2:c.-453_-452delinsT
NM_001354616.2:c.-458_-457delinsT
NM_001354617.2:c.-550_-549delinsT
NM_001354618.2:c.-550_-549delinsT
NM_001354619.2:c.-550_-549delinsT
NM_001354620.2:c.-116_-115delinsT
NM_001354621.2:c.-643_-642delinsT
NM_001354622.2:c.-756_-755delinsT
NM_001354623.2:c.-723+2786_-723+2787delinsT
NM_001354624.2:c.-653_-652delinsT
NM_001354625.2:c.-556_-555delinsT
NM_001354626.2:c.-653_-652delinsT
NM_001354627.2:c.-653_-652delinsT
NM_001354628.2:c.174_175delinsT
NM_001354629.2:c.174_175delinsT
NM_001354630.2:c.174_175delinsT
NP_000240.1:p.Leu58fs
NP_001245200.1:p.Leu58fs
NP_001341557.1:p.Leu58fs
NP_001341558.1:p.Leu58fs
NP_001341559.1:p.Leu58fs
LRG_216:g.8327_8328delinsT
NC_000003.11:g.37038167_37038168delinsT
NM_000249.3:c.174_175delGAinsT

Protein change:

L58fs

Links:

dbSNP: rs876660860

NCBI 1000 Genomes Browser:

rs876660860

Molecular consequence:

NM_001167617.3:c.-116_-115delinsT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167618.3:c.-550_-549delinsT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167619.3:c.-458_-457delinsT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258274.3:c.-695_-694delinsT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354615.2:c.-453_-452delinsT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354616.2:c.-458_-457delinsT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354617.2:c.-550_-549delinsT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354618.2:c.-550_-549delinsT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354619.2:c.-550_-549delinsT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354620.2:c.-116_-115delinsT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354621.2:c.-643_-642delinsT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354622.2:c.-756_-755delinsT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354624.2:c.-653_-652delinsT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354625.2:c.-556_-555delinsT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354626.2:c.-653_-652delinsT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354627.2:c.-653_-652delinsT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000249.4:c.174_175delinsT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258271.2:c.174_175delinsT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354628.2:c.174_175delinsT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354629.2:c.174_175delinsT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354630.2:c.174_175delinsT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258273.2:c.-517+3013_-517+3014delinsT - intron variant - [Sequence Ontology: SO:0001627]
NM_001354623.2:c.-723+2786_-723+2787delinsT - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Lynch syndrome
Identifiers:: MONDO: MONDO:0005835; MedGen: C4552100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000696124	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Mar 20, 2017)	germline	clinical testing	LabCorp Variant Classification Summary - May 2015.docx Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000696124

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Mar 20, 2017)

germline

clinical testing

LabCorp Variant Classification Summary - May 2015.docx

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

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000696124.1

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

Description

Variant summary: The MLH1 c.174_175delinsT (p.Leu58Phefs) variant results in a premature termination codon, predicted to cause a truncated or absent MLH1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.178C>T, p.Gln60X; c.298C>T, p.Arg100X; c.184_194del, p.Gln62Hisfs). This variant is absent from 121356 control chromosomes (ExAC dataset). In addition, one clinical diagnostic laboratory classified this variant as pathogenic. Taken together, this variant is classified as Likely Pathogenic.

#	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 1, 2024

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