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.583A>T (p.Lys195Ter)

Help
Interpretation:
Pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
4 (Most recent: Nov 30, 2020)
Last evaluated:
Jan 15, 2020
Accession:
VCV000218025.6
Variation ID:
218025
Description:
single nucleotide variant
Help

NM_000249.4(MLH1):c.583A>T (p.Lys195Ter)

Allele ID
214631
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
3p22.2
Genomic location
3: 37011857 (GRCh38) GRCh38 UCSC
3: 37053348 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_216:g.23508A>T
LRG_216t1:c.583A>T LRG_216p1:p.Lys195Ter
NM_000249.3:c.583A>T NP_000240.1:p.Lys195Ter nonsense
... more HGVS
Protein change
K195*, K162*, K97*
Other names
-
Canonical SPDI
NC_000003.12:37011856:A:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA279752
dbSNP: rs863225383
VarSome
Help

Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 2 criteria provided, multiple submitters, no conflicts Jan 15, 2020 RCV000216838.3
Pathogenic 2 criteria provided, single submitter Oct 31, 2017 RCV000202144.1
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
(Jul 12, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000278462.5
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (3)
Comment:
The p.K195* pathogenic mutation (also known as c.583A>T), located in coding exon 7 of the MLH1 gene, results from an A to T substitution at … (more)
Pathogenic
(Oct 31, 2017)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000779388.1
Submitted: (Jan 29, 2019)
Evidence details
Comment:
This variant is denoted MLH1 c.583A>T at the cDNA level and p.Lys195Ter (K195X) at the protein level. The substitution creates a nonsense variant, which changes … (more)
Pathogenic
(Jan 15, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV000908609.2
Submitted: (May 19, 2020)
Comment:
This variant changes 1 nucleotide in exon 7 of the MLH1 gene, creating a premature translation stop signal. This variant is expected to result in … (more)
Evidence details
Likely pathogenic
(-)
no assertion criteria provided
Method: research
not provided
Allele origin: unknown
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000257105.1
Submitted: (Nov 19, 2015)
Evidence details

Functional evidence

Help
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

Help
Title Author Journal Year Link
Genomic and transcriptomic heterogeneity of colorectal tumours arising in Lynch syndrome. Binder H The Journal of pathology 2017 PMID: 28727142
Functional testing strategy for coding genetic variants of unclear significance in MLH1 in Lynch syndrome diagnosis. Hinrichsen I Carcinogenesis 2015 PMID: 25477341
Reduced migration of MLH1 deficient colon cancer cells depends on SPTAN1. Hinrichsen I Molecular cancer 2014 PMID: 24456667

Text-mined citations for rs863225383...

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 Oct 24, 2021