Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation

ClinVar Genomic variation as it relates to human health

Advanced search

NM_000249.4(MLH1):c.156del (p.Glu53fs)

Help
Interpretation:
Pathogenic​

Review status:
reviewed by expert panel
Submissions:
6 (Most recent: Jan 7, 2021)
Last evaluated:
Sep 5, 2013
Accession:
VCV000089793.6
Variation ID:
89793
Description:
1bp deletion
Help

NM_000249.4(MLH1):c.156del (p.Glu53fs)

Allele ID
95267
Variant type
Deletion
Variant length
1 bp
Cytogenetic location
3p22.2
Genomic location
3: 36996656 (GRCh38) GRCh38 UCSC
3: 37038147 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_216:g.8309del
NM_000249.3:c.156delA
NC_000003.11:g.37038149del
... more HGVS
Protein change
E53fs
Other names
-
Canonical SPDI
NC_000003.12:36996655:AAA:AA
Functional consequence
Unknown function
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA005951
dbSNP: rs63750028
VarSome
Help

Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 2 reviewed by expert panel Sep 5, 2013 RCV000075267.2
Pathogenic 1 criteria provided, single submitter Jun 5, 2018 RCV000213962.2
Pathogenic 1 criteria provided, single submitter Mar 5, 2020 RCV000533345.4
Pathogenic 1 criteria provided, single submitter Aug 23, 2019 RCV001027534.1
Likely pathogenic 1 no assertion criteria provided - RCV000582660.1
Help
Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
MLH1 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
3503 3539

Submitted interpretations and evidence

Help
Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Sep 05, 2013)
reviewed by expert panel
Method: research
Lynch Syndrome
Allele origin: germline
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)
Accession: SCV000106261.2
Submitted: (Dec 18, 2013)
Comment:
Classified with v1.9 guidelines: https://docs.google.com/file/d/0B3JL6rP6JzhoN2EydHRVMEI1UGs
Evidence details
Comment:
Coding sequence variation resulting in a stop codon
Likely pathogenic
(Jan 19, 2017)
criteria provided, single submitter
Method: clinical testing
Hereditary nonpolyposis colon cancer
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000696118.1
Submitted: (Jan 25, 2018)
Evidence details
Comment:
Variant summary: The MLH1 c.156delA (p.Glu53Argfs) variant results in a premature termination codon, predicted to cause a truncated or absent MLH1 protein due to nonsense … (more)
Pathogenic
(Jun 05, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000276778.5
Submitted: (Nov 30, 2020)
Evidence details
Comment:
The c.156delA pathogenic mutation, located in coding exon 2 of the MLH1 gene, results from a deletion of one nucleotide at nucleotide position 156, causing … (more)
Pathogenic
(Mar 05, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary nonpolyposis colorectal neoplasms
Allele origin: germline
Invitae
Accession: SCV000625082.4
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (3)
Comment:
This sequence change creates a premature translational stop signal (p.Glu53Argfs*4) in the MLH1 gene. It is expected to result in an absent or disrupted protein … (more)
Pathogenic
(Aug 23, 2019)
criteria provided, single submitter
Method: clinical testing
Lynch syndrome II
(Autosomal dominant inheritance)
Allele origin: germline
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics
Accession: SCV001161674.1
Submitted: (Mar 13, 2020)
Evidence details
Comment:
The heterozygous deletion c.156delA (p.Glu53ArgfsTer4) lies in exon 2 of the MLH1 gene and is predicted to cause a frameshift and consequent premature termination of … (more)
Likely pathogenic
(-)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: unknown
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000691841.1
Submitted: (Oct 31, 2017)
Evidence details

Functional evidence

Help
Functional consequence Method Result Submitter Supporting information
Unknown function
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics
Accession: SCV001161674.1
Submitted: (Mar 13, 2020)
Evidence details

Citations for this variant

Help
Title Author Journal Year Link
Multigene Panel Testing Provides a New Perspective on Lynch Syndrome. Espenschied CR Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2017 PMID: 28514183
Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database. Thompson BA Nature genetics 2014 PMID: 24362816
Conversion analysis for mutation detection in MLH1 and MSH2 in patients with colorectal cancer. Casey G JAMA 2005 PMID: 15713769
http://www.insight-database.org/classifications/index.html?gene=MLH1&variant=c.156del - - - -

Text-mined citations for rs63750028...

Help
These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 27, 2021