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NM_000249.4(MLH1):c.143A>C (p.Gln48Pro)

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Interpretation:
Likely pathogenic​

Review status:
reviewed by expert panel
Submissions:
2 (Most recent: Jan 7, 2021)
Last evaluated:
Jun 21, 2019
Accession:
VCV000089739.4
Variation ID:
89739
Description:
single nucleotide variant
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NM_000249.4(MLH1):c.143A>C (p.Gln48Pro)

Allele ID
95213
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
3p22.2
Genomic location
3: 36996645 (GRCh38) GRCh38 UCSC
3: 37038136 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000003.11:g.37038136A>C
NM_000249.3:c.143A>C NP_000240.1:p.Gln48Pro missense
LRG_216:g.8296A>C
... more HGVS
Protein change
Q48P
Other names
-
Canonical SPDI
NC_000003.12:36996644:A:C
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA005432
dbSNP: rs587778914
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 RCV000075213.3
Pathogenic 1 criteria provided, single submitter Dec 19, 2019 RCV001069994.2
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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
Likely pathogenic
(Jun 21, 2019)
reviewed by expert panel
Method: curation
Lynch syndrome
Allele origin: germline
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)
Accession: SCV000106205.3
Submitted: (Jun 21, 2019)
Evidence details
Other databases
http://www.insight-database.org/…
Comment:
Multifactorial likelihood analysis posterior probability 0.95-0.99
Pathogenic
(Dec 19, 2019)
criteria provided, single submitter
Method: clinical testing
Hereditary nonpolyposis colorectal neoplasms
Allele origin: germline
Invitae
Accession: SCV001235200.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (2)
Comment:
This sequence change replaces glutamine with proline at codon 48 of the MLH1 protein (p.Gln48Pro). The glutamine residue is highly conserved and there is a … (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
Q48P mutation in the hMLH1 gene associated with Lynch syndrome in three Hungarian families. Tanyi M Familial cancer 2012 PMID: 22395473
Missense variants in hMLH1 identified in patients from the German HNPCC consortium and functional studies. Hardt K Familial cancer 2011 PMID: 21404117
http://www.insight-database.org/classifications/?gene=MLH1&variant=c.143A%3EC - - - -

Text-mined citations for rs587778914...

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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 Oct 30, 2021