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NM_000249.4(MLH1):c.1558+1G>A

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
4 (Most recent: May 26, 2021)
Last evaluated:
Aug 24, 2020
Accession:
VCV000220185.9
Variation ID:
220185
Description:
single nucleotide variant
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NM_000249.4(MLH1):c.1558+1G>A

Allele ID
221403
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
3p22.2
Genomic location
3: 37028933 (GRCh38) GRCh38 UCSC
3: 37070424 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000003.11:g.37070424G>A
LRG_216:g.40584G>A
LRG_216t1:c.1558+1G>A
... more HGVS
Protein change
-
Other names
-
Canonical SPDI
NC_000003.12:37028932:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA348840
dbSNP: rs267607832
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 1 criteria provided, single submitter Aug 24, 2020 RCV000204627.5
Pathogenic 1 criteria provided, single submitter Mar 12, 2019 RCV000223493.2
Likely pathogenic 1 criteria provided, single submitter Sep 27, 2018 RCV000781542.1
Likely pathogenic 1 criteria provided, single submitter Aug 8, 2019 RCV001507621.2
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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
Pathogenic
(Mar 12, 2019)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000274273.5
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (1)
Comment:
The c.1558+1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide after coding exon 13 of the MLH1 gene. This alteration has … (more)
Pathogenic
(Aug 24, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary nonpolyposis colorectal neoplasms
Allele origin: germline
Invitae
Accession: SCV000260539.5
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (5)
Comment:
This sequence change affects a donor splice site in intron 13 of the MLH1 gene. It is expected to disrupt RNA splicing and likely results … (more)
Likely pathogenic
(Sep 27, 2018)
criteria provided, single submitter
Method: clinical testing
Lynch syndrome
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000919662.1
Submitted: (Apr 24, 2019)
Evidence details
Comment:
Variant summary: MLH1 c.1558+1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to … (more)
Likely pathogenic
(Aug 08, 2019)
criteria provided, single submitter
Method: clinical testing
Not provided
Allele origin: germline
Mayo Clinic Laboratories,Mayo Clinic
Accession: SCV001713277.1
Submitted: (May 26, 2021)
Evidence details
Comment:
PVS1, PM2

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
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
Identification and surveillance of 19 Lynch syndrome families in southern Italy: report of six novel germline mutations and a common founder mutation. Lastella P Familial cancer 2011 PMID: 21286823
Splicing in action: assessing disease causing sequence changes. Baralle D Journal of medical genetics 2005 PMID: 16199547
Conversion analysis for mutation detection in MLH1 and MSH2 in patients with colorectal cancer. Casey G JAMA 2005 PMID: 15713769
Hereditary nonpolyposis colorectal cancer: an approach to the selection of candidates to genetic testing based on clinical and molecular characteristics. Viel A Community genetics 1998 PMID: 15178966
Small bowel carcinoma in hereditary nonpolyposis colorectal cancer. Benatti P The American journal of gastroenterology 1998 PMID: 9820400

Text-mined citations for rs267607832...

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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 Dec 02, 2021