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NM_000249.4(MLH1):c.1990-1G>C

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
4 (Most recent: Jan 7, 2021)
Last evaluated:
Oct 12, 2020
Accession:
VCV000628266.7
Variation ID:
628266
Description:
single nucleotide variant
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NM_000249.4(MLH1):c.1990-1G>C

Allele ID
619168
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
3p22.2
Genomic location
3: 37048903 (GRCh38) GRCh38 UCSC
3: 37090394 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_216:g.60554G>C
LRG_216t1:c.1990-1G>C
NC_000003.11:g.37090394G>C
... more HGVS
Protein change
-
Other names
-
Canonical SPDI
NC_000003.12:37048902:G:C
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
dbSNP: rs267607884
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic/Likely pathogenic 2 criteria provided, multiple submitters, no conflicts Sep 27, 2019 RCV000772614.3
Pathogenic 1 criteria provided, single submitter Oct 12, 2020 RCV001036557.2
Pathogenic 1 criteria provided, single submitter Apr 2, 2020 RCV001310199.1
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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
(Sep 27, 2019)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV000905795.2
Submitted: (May 19, 2020)
Comment:
This variant causes a G>C nucleotide substitution at the -1 position of intron 17 of the MLH1 gene. Splice site prediction tools predict that this … (more)
Evidence details
Pathogenic
(Feb 07, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV001174619.2
Submitted: (Nov 30, 2020)
Evidence details
Comment:
The c.1990-1G>C intronic pathogenic mutation results from a G to C substitution one nucleotide upstream from coding exon 18 of the MLH1 gene. <span style="background-color:initial">A … (more)
Pathogenic
(Apr 02, 2020)
criteria provided, single submitter
Method: clinical testing
Lynch syndrome I
Allele origin: germline
Department of Molecular Diagnostics, Institute of Oncology Ljubljana
Accession: SCV001499800.1
Submitted: (Dec 10, 2020)
Evidence details
Pathogenic
(Oct 12, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary nonpolyposis colorectal neoplasms
Allele origin: germline
Invitae
Accession: SCV001199927.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (4)
Comment:
This sequence change affects an acceptor splice site in intron 17 of the MLH1 gene. It is expected to disrupt RNA splicing and likely results … (more)

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
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
Ten novel MSH2 and MLH1 germline mutations in families with HNPCC. Krüger S Human mutation 2004 PMID: 15365996

Text-mined citations for rs267607884...

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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