NM_000249.4(MLH1):c.208-5_262del AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 3, 2019
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:: RCV001014374.3

Allele description [Variation Report for NM_000249.4(MLH1):c.208-5_262del]

NM_000249.4(MLH1):c.208-5_262del

Gene:

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

Variant type:

Deletion

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000249.4(MLH1):c.208-5_262del

HGVS:

NC_000003.12:g.37000950_37001009del
NG_007109.2:g.12601_12660del
NM_000249.4:c.208-5_262delMANE SELECT
NM_001167617.3:c.-82-5_-28del
NM_001167618.3:c.-516-5_-462del
NM_001167619.3:c.-424-5_-370del
NM_001258271.2:c.208-5_262del
NM_001258273.2:c.-516-5_-462del
NM_001258274.3:c.-516-5_-462del
NM_001354615.2:c.-419-5_-365del
NM_001354616.2:c.-424-5_-370del
NM_001354617.2:c.-516-5_-462del
NM_001354618.2:c.-516-5_-462del
NM_001354619.2:c.-516-5_-462del
NM_001354620.2:c.-82-5_-28del
NM_001354621.2:c.-609-5_-555del
NM_001354622.2:c.-722-5_-668del
NM_001354623.2:c.-722-5_-668del
NM_001354624.2:c.-619-5_-565del
NM_001354625.2:c.-522-5_-468del
NM_001354626.2:c.-619-5_-565del
NM_001354627.2:c.-619-5_-565del
NM_001354628.2:c.208-5_262del
NM_001354629.2:c.208-3451_208-3392del
NM_001354630.2:c.208-5_262del
LRG_216t1:c.208-5_262del60
LRG_216:g.12601_12660del
NC_000003.11:g.37042441_37042500del
NM_000249.3:c.208-5_262del60

Links:

dbSNP: rs1575413885

NCBI 1000 Genomes Browser:

rs1575413885

Molecular consequence:

NM_001354629.2:c.208-3451_208-3392del - intron variant - [Sequence Ontology: SO:0001627]
NM_000249.4:c.208-5_262del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001167617.3:c.-82-5_-28del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001167618.3:c.-516-5_-462del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001167619.3:c.-424-5_-370del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001258271.2:c.208-5_262del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001258273.2:c.-516-5_-462del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001258274.3:c.-516-5_-462del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354615.2:c.-419-5_-365del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354616.2:c.-424-5_-370del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354617.2:c.-516-5_-462del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354618.2:c.-516-5_-462del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354619.2:c.-516-5_-462del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354620.2:c.-82-5_-28del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354621.2:c.-609-5_-555del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354622.2:c.-722-5_-668del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354623.2:c.-722-5_-668del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354624.2:c.-619-5_-565del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354625.2:c.-522-5_-468del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354626.2:c.-619-5_-565del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354627.2:c.-619-5_-565del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354628.2:c.208-5_262del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354630.2:c.208-5_262del - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001175072	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jun 3, 2019)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001175072

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jun 3, 2019)

germline

clinical testing

Citation Link

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

Details of each submission

From Ambry Genetics, SCV001175072.4

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

Description

The c.208-5_262DEL60 pathogenic mutation, which spans from intron 2 through coding exon 3 of the MLH1 gene, results from a deletion of 60 nucleotides at positions c.208-5 to c.262, including 55bp of coding sequence. Both out-of-frame deletions and alterations that disrupt the canonical splice site are expected to result in an abnormal transcript or a transcript that is subject to nonsense-mediated mRNA decay and the production of no functional protein. As such, this alteration is interpreted as a disease-causing mutation.

#	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: May 1, 2024

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