NM_000249.4(MLH1):c.1783_1784del (p.Ser595fs) AND Colorectal cancer, hereditary nonpolyposis, type 2

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jul 24, 2023
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:: RCV000018638.32

Allele description [Variation Report for NM_000249.4(MLH1):c.1783_1784del (p.Ser595fs)]

NM_000249.4(MLH1):c.1783_1784del (p.Ser595fs)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000249.4(MLH1):c.1783_1784del (p.Ser595fs)

HGVS:

NC_000003.12:g.37047566AG[2]
NG_007109.2:g.59217AG[2]
NM_000249.4:c.1783_1784delMANE SELECT
NM_001167617.3:c.1489_1490del
NM_001167618.3:c.1060_1061del
NM_001167619.3:c.1060_1061del
NM_001258271.2:c.1783_1784del
NM_001258273.2:c.1060_1061del
NM_001258274.3:c.1060_1061del
NM_001354615.2:c.1060_1061del
NM_001354616.2:c.1060_1061del
NM_001354617.2:c.1060_1061del
NM_001354618.2:c.1060_1061del
NM_001354619.2:c.1060_1061del
NM_001354620.2:c.1489_1490del
NM_001354621.2:c.760_761del
NM_001354622.2:c.760_761del
NM_001354623.2:c.760_761del
NM_001354624.2:c.709_710del
NM_001354625.2:c.709_710del
NM_001354626.2:c.709_710del
NM_001354627.2:c.709_710del
NM_001354628.2:c.1783_1784del
NM_001354629.2:c.1684_1685del
NM_001354630.2:c.1732-951AG[2]
NP_000240.1:p.Ser595fs
NP_001161089.1:p.Ser497fs
NP_001161090.1:p.Ser354fs
NP_001161091.1:p.Ser354fs
NP_001245200.1:p.Ser595fs
NP_001245202.1:p.Ser354fs
NP_001245203.1:p.Ser354fs
NP_001341544.1:p.Ser354fs
NP_001341545.1:p.Ser354fs
NP_001341546.1:p.Ser354fs
NP_001341547.1:p.Ser354fs
NP_001341548.1:p.Ser354fs
NP_001341549.1:p.Ser497fs
NP_001341550.1:p.Ser254fs
NP_001341551.1:p.Ser254fs
NP_001341552.1:p.Ser254fs
NP_001341553.1:p.Ser237fs
NP_001341554.1:p.Ser237fs
NP_001341555.1:p.Ser237fs
NP_001341556.1:p.Ser237fs
NP_001341557.1:p.Ser595fs
NP_001341558.1:p.Ser562fs
LRG_216:g.59217AG[2]
NC_000003.11:g.37089057AG[2]
NC_000003.11:g.37089057_37089058del
NM_000249.3:c.1783_1784delAG

Protein change:

S237fs

Links:

LOVD 3: MLH1_001602; OMIM: 120436.0027; dbSNP: rs63750035

NCBI 1000 Genomes Browser:

rs63750035

Molecular consequence:

NM_000249.4:c.1783_1784del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001167617.3:c.1489_1490del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001167618.3:c.1060_1061del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001167619.3:c.1060_1061del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258271.2:c.1783_1784del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258273.2:c.1060_1061del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258274.3:c.1060_1061del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354615.2:c.1060_1061del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354616.2:c.1060_1061del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354617.2:c.1060_1061del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354618.2:c.1060_1061del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354619.2:c.1060_1061del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354620.2:c.1489_1490del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354621.2:c.760_761del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354622.2:c.760_761del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354623.2:c.760_761del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354624.2:c.709_710del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354625.2:c.709_710del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354626.2:c.709_710del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354627.2:c.709_710del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354628.2:c.1783_1784del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354629.2:c.1684_1685del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354630.2:c.1732-951AG[2] - intron variant - [Sequence Ontology: SO:0001627]

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

Recent activity

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sex hormone-binding globulin isoform 5 [Homo sapiens]
sex hormone-binding globulin isoform 5 [Homo sapiens]
gi|574287947|ref|NP_001276043.1|

Protein
Prox1 prospero homeobox 1 [Rattus norvegicus]
Prox1 prospero homeobox 1 [Rattus norvegicus]
Gene ID:305066

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002601715	OMIM	no assertion criteria provided	Pathogenic (Jun 1, 2007)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV004190028	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Pathogenic (Jul 24, 2023)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002601715

OMIM

no assertion criteria provided

Pathogenic
(Jun 1, 2007)

germline

literature only

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

SCV004190028

Myriad Genetics, Inc.

criteria provided, single submitter

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

Pathogenic
(Jul 24, 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	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Biallelic germline mutations of mismatch-repair genes: a possible cause for multiple pediatric malignancies.

Poley JW, Wagner A, Hoogmans MM, Menko FH, Tops C, Kros JM, Reddingius RE, Meijers-Heijboer H, Kuipers EJ, Dinjens WN; Rotterdam Initiative on Gastrointestinal Hereditary Tumors..

Cancer. 2007 Jun 1;109(11):2349-56.

PubMed [citation]

PMID:: 17440981

Details of each submission

From OMIM, SCV002601715.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a 4-year-old boy (case I) with glioblastoma, nephroblastoma, and cafe-au-lait spots consistent with mismatch repair cancer syndrome (MMRCS1; 276300), Poley et al. (2007) identified compound heterozygosity for 2 mutations in the MLH1 gene: a 2-bp deletion (593delAG) and a met35-to-asn (M35N; 120436.0028) substitution. Both tumors and normal tissue were negative for the MLH1 protein. The nephroblastoma showed microsatellite instability, but the glioblastoma did not. Both parents, who were each heterozygous for a respective mutation, came from families with HNPCC2 (LYNCH2; 609310).

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

From Myriad Genetics, Inc., SCV004190028.1

#	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 considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

#	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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