NM_000249.4(MLH1):c.721A>G (p.Lys241Glu) AND Colorectal cancer, hereditary nonpolyposis, type 2

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Mar 14, 2023
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:: RCV000662556.2

Allele description [Variation Report for NM_000249.4(MLH1):c.721A>G (p.Lys241Glu)]

NM_000249.4(MLH1):c.721A>G (p.Lys241Glu)

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.721A>G (p.Lys241Glu)

HGVS:

NC_000003.12:g.37014475A>G
NG_007109.2:g.26126A>G
NM_000249.4:c.721A>GMANE SELECT
NM_001167617.3:c.427A>G
NM_001167618.3:c.-3A>G
NM_001167619.3:c.-3A>G
NM_001258271.2:c.721A>G
NM_001258273.2:c.-3A>G
NM_001258274.3:c.-3A>G
NM_001354615.2:c.-3A>G
NM_001354616.2:c.-3A>G
NM_001354617.2:c.-3A>G
NM_001354618.2:c.-3A>G
NM_001354619.2:c.-3A>G
NM_001354620.2:c.427A>G
NM_001354621.2:c.-140+2376A>G
NM_001354622.2:c.-209A>G
NM_001354623.2:c.-209A>G
NM_001354624.2:c.-106A>G
NM_001354625.2:c.-106A>G
NM_001354626.2:c.-106A>G
NM_001354627.2:c.-106A>G
NM_001354628.2:c.721A>G
NM_001354629.2:c.622A>G
NM_001354630.2:c.721A>G
NP_000240.1:p.Lys241Glu
NP_000240.1:p.Lys241Glu
NP_001161089.1:p.Lys143Glu
NP_001245200.1:p.Lys241Glu
NP_001341549.1:p.Lys143Glu
NP_001341557.1:p.Lys241Glu
NP_001341558.1:p.Lys208Glu
NP_001341559.1:p.Lys241Glu
LRG_216t1:c.721A>G
LRG_216:g.26126A>G
LRG_216p1:p.Lys241Glu
NC_000003.11:g.37055966A>G
NM_000249.3:c.721A>G

Protein change:

K143E

Links:

dbSNP: rs587778447

NCBI 1000 Genomes Browser:

rs587778447

Molecular consequence:

NM_001167618.3:c.-3A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167619.3:c.-3A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258273.2:c.-3A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258274.3:c.-3A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354615.2:c.-3A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354616.2:c.-3A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354617.2:c.-3A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354618.2:c.-3A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354619.2:c.-3A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354622.2:c.-209A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354623.2:c.-209A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354624.2:c.-106A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354625.2:c.-106A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354626.2:c.-106A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354627.2:c.-106A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354621.2:c.-140+2376A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000249.4:c.721A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001167617.3:c.427A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001258271.2:c.721A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354620.2:c.427A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354628.2:c.721A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354629.2:c.622A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354630.2:c.721A>G - 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
SCV000785146	Counsyl	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015))	Uncertain significance (May 12, 2017)	unknown	clinical testing	Counsyl_Autosomal_Dominant_Disease_Classification_criteria_(2015)_v1.pdf, Citation Link,
SCV004018155	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Uncertain significance (Mar 14, 2023)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000785146

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Dominant Disease Classification criteria (2015))

Uncertain significance
(May 12, 2017)

unknown

clinical testing

Counsyl_Autosomal_Dominant_Disease_Classification_criteria_(2015)_v1.pdf,

Citation Link,

SCV004018155

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))

Uncertain significance
(Mar 14, 2023)

unknown

clinical testing

Citation Link

Help

Summary from all submissions

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

Details of each submission

From Counsyl, SCV000785146.2

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

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

From Myriad Genetics, Inc., SCV004018155.1

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

Description

This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.

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

Last Updated: Sep 29, 2024

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