NM_000249.4(MLH1):c.91G>T (p.Ala31Ser) AND Colorectal cancer, hereditary nonpolyposis, type 2

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Mar 26, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001149362.6

Allele description [Variation Report for NM_000249.4(MLH1):c.91G>T (p.Ala31Ser)]

NM_000249.4(MLH1):c.91G>T (p.Ala31Ser)

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.91G>T (p.Ala31Ser)

HGVS:

NC_000003.12:g.36993638G>T
NG_007109.2:g.5289G>T
NG_008418.1:g.4667C>A
NM_000249.4:c.91G>TMANE SELECT
NM_001167617.3:c.-426G>T
NM_001167618.3:c.-855G>T
NM_001167619.3:c.-768G>T
NM_001258271.2:c.91G>T
NM_001258273.2:c.-542G>T
NM_001258274.3:c.-1005G>T
NM_001354615.2:c.-536G>T
NM_001354616.2:c.-536G>T
NM_001354617.2:c.-628G>T
NM_001354618.2:c.-860G>T
NM_001354619.2:c.-984G>T
NM_001354620.2:c.-194G>T
NM_001354621.2:c.-953G>T
NM_001354622.2:c.-1066G>T
NM_001354623.2:c.-975G>T
NM_001354624.2:c.-736G>T
NM_001354625.2:c.-634G>T
NM_001354626.2:c.-731G>T
NM_001354627.2:c.-963G>T
NM_001354628.2:c.91G>T
NM_001354629.2:c.91G>T
NM_001354630.2:c.91G>T
NP_000240.1:p.Ala31Ser
NP_001245200.1:p.Ala31Ser
NP_001341557.1:p.Ala31Ser
NP_001341558.1:p.Ala31Ser
NP_001341559.1:p.Ala31Ser
LRG_216t1:c.91G>T
LRG_216:g.5289G>T
NC_000003.11:g.37035129G>T
NM_000249.3:c.91G>T

Protein change:

A31S

Links:

dbSNP: rs749671520

NCBI 1000 Genomes Browser:

rs749671520

Molecular consequence:

NM_001167617.3:c.-426G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167618.3:c.-855G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167619.3:c.-768G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258273.2:c.-542G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258274.3:c.-1005G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354615.2:c.-536G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354616.2:c.-536G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354617.2:c.-628G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354618.2:c.-860G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354619.2:c.-984G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354620.2:c.-194G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354621.2:c.-953G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354622.2:c.-1066G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354623.2:c.-975G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354624.2:c.-736G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354625.2:c.-634G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354626.2:c.-731G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354627.2:c.-963G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000249.4:c.91G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001258271.2:c.91G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354628.2:c.91G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354629.2:c.91G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354630.2:c.91G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Colorectal cancer, hereditary nonpolyposis, type 2 (LYNCH2)
Synonyms:: COLON CANCER, FAMILIAL NONPOLYPOSIS, TYPE 2; Lynch syndrome II; MLH1-Related Lynch Syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012249; MedGen: C1333991; Orphanet: 144; OMIM: 609310

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001310308	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Apr 28, 2017)	germline	clinical testing	Citation Link,
SCV004807203	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 26, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001310308

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Apr 28, 2017)

germline

clinical testing

Citation Link,

SCV004807203

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 26, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Illumina Laboratory Services, Illumina, SCV001310308.1

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

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

#	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

From Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, SCV004807203.1

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

#	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: Sep 29, 2024

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