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NM_000249.3(MLH1):c.1219C>T (p.Gln407Ter)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
7 (Most recent: Sep 25, 2021)
Last evaluated:
Apr 21, 2020
Accession:
VCV000371799.9
Variation ID:
371799
Description:
single nucleotide variant
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NM_000249.3(MLH1):c.1219C>T (p.Gln407Ter)

Allele ID
358744
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
3p22.2
Genomic location
3: 37025817 (GRCh38) GRCh38 UCSC
3: 37067308 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_216:g.37468C>T
NC_000003.11:g.37067308C>T
NC_000003.12:g.37025817C>T
... more HGVS
Protein change
Q407*, Q49*, Q166*, Q309*, Q374*, Q66*
Other names
-
Canonical SPDI
NC_000003.12:37025816:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA16042072
dbSNP: rs1057517541
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 3 criteria provided, multiple submitters, no conflicts Apr 21, 2020 RCV000486818.4
Likely pathogenic 1 criteria provided, single submitter Dec 7, 2015 RCV000411311.1
Pathogenic 1 criteria provided, single submitter Sep 5, 2017 RCV000464749.5
Pathogenic 1 criteria provided, single submitter Nov 20, 2018 RCV000684819.2
Pathogenic 1 criteria provided, single submitter Jan 15, 2020 RCV001183269.1
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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
3488 3523

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Dec 07, 2015)
criteria provided, single submitter
Method: clinical testing
Lynch syndrome II
Allele origin: unknown
Counsyl
Accession: SCV000487919.1
Submitted: (Nov 23, 2016)
Evidence details
Publications
PubMed (1)
Pathogenic
(Nov 20, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary nonpolyposis colon cancer
Allele origin: germline
Invitae
Accession: SCV000543574.4
Submitted: (Mar 28, 2019)
Evidence details
Publications
PubMed (2)
Comment:
This sequence change creates a premature translational stop signal (p.Gln407*) in the MLH1 gene. It is expected to result in an absent or disrupted protein … (more)
Pathogenic
(Apr 21, 2020)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000571217.4
Submitted: (Sep 25, 2021)
Evidence details
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not … (more)
Pathogenic
(Sep 05, 2017)
criteria provided, single submitter
Method: clinical testing
Lynch syndrome
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000919637.1
Submitted: (Apr 24, 2019)
Evidence details
Publications
PubMed (1)
Comment:
Variant summary: The MLH1 c.1219C>T (p.Gln407X) variant results in a premature termination codon, predicted to cause a truncated or absent MLH1 protein due to nonsense … (more)
Pathogenic
(Oct 07, 2018)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV001134288.2
Submitted: (Mar 06, 2020)
Evidence details
Publications
PubMed (1)
Comment:
The variant creates a premature nonsense codon, and is therefore predicted to significantly disrupt the protein structure. Found in at least one symptomatic patient, and … (more)
Pathogenic
(Jan 15, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV001348953.1
Submitted: (May 19, 2020)
Comment:
This variant changes 1 nucleotide in exon 12 of the MLH1 gene, creating a premature translation stop signal. This variant is expected to result in … (more)
Evidence details
Pathogenic
(-)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: unknown
Department of Pathology and Laboratory Medicine,Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000592401.2
Submitted: (Mar 31, 2021)
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
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Mismatch repair gene mutation spectrum in the Swedish Lynch syndrome population. Lagerstedt-Robinson K Oncology reports 2016 PMID: 27601186
Mutation spectrum and risk of colorectal cancer in African American families with Lynch syndrome. Guindalini RS Gastroenterology 2015 PMID: 26248088

Text-mined citations for rs1057517541...

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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 Sep 26, 2021