NM_000249.4(MLH1):c.592G>T (p.Gly198Ter) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 15, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001874494.3

Allele description [Variation Report for NM_000249.4(MLH1):c.592G>T (p.Gly198Ter)]

NM_000249.4(MLH1):c.592G>T (p.Gly198Ter)

Gene:

MLH1:mutL homolog 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000249.4(MLH1):c.592G>T (p.Gly198Ter)

HGVS:

NC_000003.12:g.37012014G>T
NG_007109.2:g.23665G>T
NM_000249.4:c.592G>TMANE SELECT
NM_001167617.3:c.298G>T
NM_001167618.3:c.-132G>T
NM_001167619.3:c.-132G>T
NM_001258271.2:c.592G>T
NM_001258273.2:c.-132G>T
NM_001258274.3:c.-132G>T
NM_001354615.2:c.-132G>T
NM_001354616.2:c.-132G>T
NM_001354617.2:c.-132G>T
NM_001354618.2:c.-132G>T
NM_001354619.2:c.-132G>T
NM_001354620.2:c.298G>T
NM_001354621.2:c.-225G>T
NM_001354622.2:c.-338G>T
NM_001354623.2:c.-338G>T
NM_001354624.2:c.-235G>T
NM_001354625.2:c.-235G>T
NM_001354626.2:c.-235G>T
NM_001354627.2:c.-235G>T
NM_001354628.2:c.592G>T
NM_001354629.2:c.493G>T
NM_001354630.2:c.592G>T
NP_000240.1:p.Gly198Ter
NP_001161089.1:p.Gly100Ter
NP_001245200.1:p.Gly198Ter
NP_001341549.1:p.Gly100Ter
NP_001341557.1:p.Gly198Ter
NP_001341558.1:p.Gly165Ter
NP_001341559.1:p.Gly198Ter
LRG_216t1:c.592G>T
LRG_216:g.23665G>T
NC_000003.11:g.37053505G>T
NM_000249.3:c.592G>T

Protein change:

G100*

Links:

dbSNP: rs2125808143

NCBI 1000 Genomes Browser:

rs2125808143

Molecular consequence:

NM_001167618.3:c.-132G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167619.3:c.-132G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258273.2:c.-132G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258274.3:c.-132G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354615.2:c.-132G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354616.2:c.-132G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354617.2:c.-132G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354618.2:c.-132G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354619.2:c.-132G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354621.2:c.-225G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354622.2:c.-338G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354623.2:c.-338G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354624.2:c.-235G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354625.2:c.-235G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354626.2:c.-235G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354627.2:c.-235G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000249.4:c.592G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001167617.3:c.298G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001258271.2:c.592G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001354620.2:c.298G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001354628.2:c.592G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001354629.2:c.493G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001354630.2:c.592G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Hereditary nonpolyposis colorectal neoplasms
Identifiers:: MeSH: D003123; MedGen: C0009405

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002136273	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 15, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 15713769, 24362816, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002136273

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 15, 2021)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Conversion analysis for mutation detection in MLH1 and MSH2 in patients with colorectal cancer.

Casey G, Lindor NM, Papadopoulos N, Thibodeau SN, Moskow J, Steelman S, Buzin CH, Sommer SS, Collins CE, Butz M, Aronson M, Gallinger S, Barker MA, Young JP, Jass JR, Hopper JL, Diep A, Bapat B, Salem M, Seminara D, Haile R; Colon Cancer Family Registry..

JAMA. 2005 Feb 16;293(7):799-809.

PubMed [citation]

PMID:: 15713769
PMCID:: PMC2933041

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, Spurdle AB, Plazzer JP, Greenblatt MS, Akagi K, Al-Mulla F, Bapat B, Bernstein I, Capellá G, den Dunnen JT, du Sart D, Fabre A, Farrell MP, Farrington SM, Frayling IM, Frebourg T, Goldgar DE, Heinen CD, Holinski-Feder E, Kohonen-Corish M, Robinson KL, Leung SY, et al.

Nat Genet. 2014 Feb;46(2):107-115. doi: 10.1038/ng.2854. Epub 2013 Dec 22.

PubMed [citation]

PMID:: 24362816
PMCID:: PMC4294709

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV002136273.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with MLH1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gly198*) in the MLH1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MLH1 are known to be pathogenic (PMID: 15713769, 24362816).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 1, 2024

ClinVar

Relating variation to medicine