U.S. flag

An official website of the United States government

NM_000249.4(MLH1):c.244A>G (p.Thr82Ala) AND Carcinoma of colon

Germline classification:
Pathogenic (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:
RCV001353582.1

Allele description [Variation Report for NM_000249.4(MLH1):c.244A>G (p.Thr82Ala)]

NM_000249.4(MLH1):c.244A>G (p.Thr82Ala)

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.244A>G (p.Thr82Ala)
HGVS:
  • NC_000003.12:g.37000991A>G
  • NG_007109.2:g.12642A>G
  • NM_000249.4:c.244A>GMANE SELECT
  • NM_001167617.3:c.-46A>G
  • NM_001167618.3:c.-480A>G
  • NM_001167619.3:c.-388A>G
  • NM_001258271.2:c.244A>G
  • NM_001258273.2:c.-480A>G
  • NM_001258274.3:c.-480A>G
  • NM_001354615.2:c.-383A>G
  • NM_001354616.2:c.-388A>G
  • NM_001354617.2:c.-480A>G
  • NM_001354618.2:c.-480A>G
  • NM_001354619.2:c.-480A>G
  • NM_001354620.2:c.-46A>G
  • NM_001354621.2:c.-573A>G
  • NM_001354622.2:c.-686A>G
  • NM_001354623.2:c.-686A>G
  • NM_001354624.2:c.-583A>G
  • NM_001354625.2:c.-486A>G
  • NM_001354626.2:c.-583A>G
  • NM_001354627.2:c.-583A>G
  • NM_001354628.2:c.244A>G
  • NM_001354629.2:c.208-3410A>G
  • NM_001354630.2:c.244A>G
  • NP_000240.1:p.Thr82Ala
  • NP_000240.1:p.Thr82Ala
  • NP_001245200.1:p.Thr82Ala
  • NP_001341557.1:p.Thr82Ala
  • NP_001341559.1:p.Thr82Ala
  • LRG_216t1:c.244A>G
  • LRG_216:g.12642A>G
  • LRG_216p1:p.Thr82Ala
  • NC_000003.11:g.37042482A>G
  • NM_000249.3:c.244A>G
  • NM_001167617.1:c.-46A>G
  • p.T82A
Protein change:
T82A
Links:
dbSNP: rs587778998
NCBI 1000 Genomes Browser:
rs587778998
Molecular consequence:
  • NM_001167617.3:c.-46A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001167618.3:c.-480A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001167619.3:c.-388A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001258273.2:c.-480A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001258274.3:c.-480A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354615.2:c.-383A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354616.2:c.-388A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354617.2:c.-480A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354618.2:c.-480A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354619.2:c.-480A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354620.2:c.-46A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354621.2:c.-573A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354622.2:c.-686A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354623.2:c.-686A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354624.2:c.-583A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354625.2:c.-486A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354626.2:c.-583A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354627.2:c.-583A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354629.2:c.208-3410A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000249.4:c.244A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258271.2:c.244A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354628.2:c.244A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354630.2:c.244A>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
2

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000592341Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria provided
Pathogenicunknownclinical testing

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownyes2not providednot providednot providednot providedclinical testing

Details of each submission

From Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV000592341.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testingnot provided

Description

The p.Thr82Ala variant has been previously reported in the literature and by our laboratory. It was identified in one individual who was reported to have high microsatellite instability and was MLH1 deficient. In addition, it was shown to segregate in one affected family member (Pastrello_2011_21239990). Our laboratory has identified this variant in one family and the variant segregated with disease in 5 affected individuals. Although the pattern of MSI and IHC deficient tumours was inconsistent across individuals from this family, the observation of this variant segregating with Lynch syndrome related cancers increases the likelihood this variant is pathogenic. In addition, functional studies in yeast demonstrated that different variants at this same amino acid residue (T82S, T82K, T82M) were associated with a loss of mismatch repair function between 8% and 67%, increasing the likelihood that this variant may affect normal protein function (Ellison_2004_15475387). In summary, based on the above information, this variant is classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providednot providednot provided2not providednot providednot provided

Last Updated: Nov 18, 2024