NM_000249.4(MLH1):c.292_293delinsTT (p.Gly98Phe) AND Carcinoma of colon

Germline classification:: Uncertain significance (1 submission)
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV001356181.1

Allele description [Variation Report for NM_000249.4(MLH1):c.292_293delinsTT (p.Gly98Phe)]

NM_000249.4(MLH1):c.292_293delinsTT (p.Gly98Phe)

Gene:

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

Variant type:

Indel

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000249.4(MLH1):c.292_293delinsTT (p.Gly98Phe)

HGVS:

NC_000003.12:g.37001039_37001040delinsTT
NG_007109.2:g.12690_12691delinsTT
NM_000249.4:c.292_293delinsTTMANE SELECT
NM_001167617.3:c.3_4delinsTT
NM_001167618.3:c.-432_-431delinsTT
NM_001167619.3:c.-340_-339delinsTT
NM_001258271.2:c.292_293delinsTT
NM_001258273.2:c.-432_-431delinsTT
NM_001258274.3:c.-432_-431delinsTT
NM_001354615.2:c.-335_-334delinsTT
NM_001354616.2:c.-340_-339delinsTT
NM_001354617.2:c.-432_-431delinsTT
NM_001354618.2:c.-432_-431delinsTT
NM_001354619.2:c.-432_-431delinsTT
NM_001354620.2:c.3_4delinsTT
NM_001354621.2:c.-525_-524delinsTT
NM_001354622.2:c.-638_-637delinsTT
NM_001354623.2:c.-638_-637delinsTT
NM_001354624.2:c.-535_-534delinsTT
NM_001354625.2:c.-438_-437delinsTT
NM_001354626.2:c.-535_-534delinsTT
NM_001354627.2:c.-535_-534delinsTT
NM_001354628.2:c.292_293delinsTT
NM_001354629.2:c.208-3362_208-3361delinsTT
NM_001354630.2:c.292_293delinsTT
NP_000240.1:p.Gly98Phe
NP_000240.1:p.Gly98Phe
NP_001161089.1:p.Met1_Ala2delinsIleSer
NP_001245200.1:p.Gly98Phe
NP_001341549.1:p.Met1_Ala2delinsIleSer
NP_001341557.1:p.Gly98Phe
NP_001341559.1:p.Gly98Phe
LRG_216t1:c.292_293delinsTT
LRG_216:g.12690_12691delinsTT
LRG_216p1:p.Gly98Phe
NC_000003.11:g.37042530_37042531delinsTT
NM_000249.3:c.292_293delGGinsTT
NM_000249.3:c.292_293delinsTT

Protein change:

G98F

Links:

dbSNP: rs1553640314

NCBI 1000 Genomes Browser:

rs1553640314

Molecular consequence:

NM_001167618.3:c.-432_-431delinsTT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167619.3:c.-340_-339delinsTT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258273.2:c.-432_-431delinsTT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258274.3:c.-432_-431delinsTT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354615.2:c.-335_-334delinsTT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354616.2:c.-340_-339delinsTT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354617.2:c.-432_-431delinsTT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354618.2:c.-432_-431delinsTT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354619.2:c.-432_-431delinsTT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354621.2:c.-525_-524delinsTT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354622.2:c.-638_-637delinsTT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354623.2:c.-638_-637delinsTT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354624.2:c.-535_-534delinsTT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354625.2:c.-438_-437delinsTT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354626.2:c.-535_-534delinsTT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354627.2:c.-535_-534delinsTT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167617.3:c.3_4delinsTT - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001354620.2:c.3_4delinsTT - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001354629.2:c.208-3362_208-3361delinsTT - intron variant - [Sequence Ontology: SO:0001627]
NM_000249.4:c.292_293delinsTT - missense variant - [Sequence Ontology: SO:0001583]
NM_001167617.3:c.3_4delinsTT - missense variant - [Sequence Ontology: SO:0001583]
NM_001258271.2:c.292_293delinsTT - missense variant - [Sequence Ontology: SO:0001583]
NM_001354620.2:c.3_4delinsTT - missense variant - [Sequence Ontology: SO:0001583]
NM_001354628.2:c.292_293delinsTT - missense variant - [Sequence Ontology: SO:0001583]
NM_001354630.2:c.292_293delinsTT - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Carcinoma of colon (CRC)
Synonyms:: Colonic carcinoma; Colon carcinoma
Identifiers:: MONDO: MONDO:0002032; MedGen: C0699790

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LOC129300581 [Prosopis cineraria]
LOC129300581 [Prosopis cineraria]
Gene ID:129300581

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001551272	Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR) See additional submitters Franklin by Genoox	no assertion criteria provided	Uncertain significance	unknown	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001551272

Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria provided

Uncertain significance

unknown

clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	yes	1	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV001551272.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

Description

The MLH1 p.Gly98Phe variant was not identified in the literature nor was it identified in the following databases: dbSNP, ClinVar, COGR, Cosmic, MutDB, UMD-LSDB, Insight Colon Cancer Gene Variant Database, Zhejiang Colon Cancer Database, Mismatch Repair Genes Variant Database, the Insight Hereditary Tumors Database, the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The p.Gly98 residue is conserved across mammals and other organisms, and 5 out of 5 computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and 3 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing. However, this information is not predictive enough to assume pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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

Last Updated: Sep 29, 2024

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