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NM_000249.4(MLH1):c.677+1G>A

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Interpretation:
Likely pathogenic​

Review status:
reviewed by expert panel
Submissions:
4 (Most recent: May 19, 2020)
Last evaluated:
Jun 21, 2019
Accession:
VCV000090311.3
Variation ID:
90311
Description:
single nucleotide variant
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NM_000249.4(MLH1):c.677+1G>A

Allele ID
95785
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
3p22.2
Genomic location
3: 37012100 (GRCh38) GRCh38 UCSC
3: 37053591 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_216:g.23751G>A
LRG_216t1:c.677+1G>A
NM_001354622.2:c.-253+1G>A splice donor
... more HGVS
Protein change
-
Other names
-
Canonical SPDI
NC_000003.12:37012099:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA011519
dbSNP: rs267607778
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely pathogenic 1 reviewed by expert panel Jun 21, 2019 RCV000075802.3
Pathogenic 1 criteria provided, single submitter Jun 14, 2017 RCV000533036.1
Likely pathogenic 1 criteria provided, single submitter Jun 4, 2018 RCV000663323.1
Likely pathogenic 1 criteria provided, single submitter Dec 18, 2018 RCV001183308.1
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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

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Jun 21, 2019)
reviewed by expert panel
Method: curation
Lynch syndrome
Allele origin: germline
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)
Accession: SCV000106817.3
Submitted: (Jun 21, 2019)
Evidence details
Other databases
http://www.insight-database.org/…
Comment:
Interrupts canonical donor splice site
Pathogenic
(Jun 14, 2017)
criteria provided, single submitter
Method: clinical testing
Hereditary nonpolyposis colorectal neoplasms
Allele origin: germline
Invitae
Accession: SCV000625183.1
Submitted: (Oct 05, 2017)
Evidence details
Comment:
This sequence change affects a donor splice site in intron 8 of the MLH1 gene. It is expected to disrupt RNA splicing and likely results … (more)
Likely pathogenic
(Jun 04, 2018)
criteria provided, single submitter
Method: clinical testing
Lynch syndrome II
Allele origin: unknown
Counsyl
Accession: SCV000786595.2
Submitted: (Jun 20, 2018)
Evidence details
Publications
PubMed (2)
Likely pathogenic
(Dec 18, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV001349012.1
Submitted: (May 19, 2020)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Integrative analysis of hereditary nonpolyposis colorectal cancer: the contribution of allele-specific expression and other assays to diagnostic algorithms. De Lellis L PloS one 2013 PMID: 24278394
Mismatch repair gene analysis in Catalonian families with colorectal cancer. Palicio M Journal of medical genetics 2002 PMID: 12070261
http://www.insight-database.org/classifications/?gene=MLH1&variant=c.677+1G%3EA - - - -

Text-mined citations for rs267607778...

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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