NM_000249.4(MLH1):c.147_177dup (p.Gln60delinsAspCysTer) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 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:: RCV002396912.2

Allele description [Variation Report for NM_000249.4(MLH1):c.147_177dup (p.Gln60delinsAspCysTer)]

NM_000249.4(MLH1):c.147_177dup (p.Gln60delinsAspCysTer)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000249.4(MLH1):c.147_177dup (p.Gln60delinsAspCysTer)

HGVS:

NC_000003.12:g.36996649_36996679dup
NG_007109.2:g.8300_8330dup
NG_008418.1:g.1627_1657dup
NM_000249.4:c.147_177dupMANE SELECT
NM_001167617.3:c.-143_-113dup
NM_001167618.3:c.-577_-547dup
NM_001167619.3:c.-485_-455dup
NM_001258271.2:c.147_177dup
NM_001258273.2:c.-517+2986_-517+3016dup
NM_001258274.3:c.-722_-692dup
NM_001354615.2:c.-480_-450dup
NM_001354616.2:c.-485_-455dup
NM_001354617.2:c.-577_-547dup
NM_001354618.2:c.-577_-547dup
NM_001354619.2:c.-577_-547dup
NM_001354620.2:c.-143_-113dup
NM_001354621.2:c.-670_-640dup
NM_001354622.2:c.-783_-753dup
NM_001354623.2:c.-723+2759_-723+2789dup
NM_001354624.2:c.-680_-650dup
NM_001354625.2:c.-583_-553dup
NM_001354626.2:c.-680_-650dup
NM_001354627.2:c.-680_-650dup
NM_001354628.2:c.147_177dup
NM_001354629.2:c.147_177dup
NM_001354630.2:c.147_177dup
NP_000240.1:p.Gln60Aspfs
NP_000240.1:p.Gln60delinsAspCysTer
NP_001245200.1:p.Gln60delinsAspCysTer
NP_001341557.1:p.Gln60delinsAspCysTer
NP_001341558.1:p.Gln60delinsAspCysTer
NP_001341559.1:p.Gln60delinsAspCysTer
LRG_216t1:c.147_177dup
LRG_216:g.8300_8330dup
LRG_216p1:p.Gln60Aspfs
NC_000003.11:g.37038140_37038170dup
NM_000249.3:c.147_177dup
NM_000249.3:c.147_177dupGATTGTTAAAGAGGGAGGCCTGAAGTTGATT

Molecular consequence:

NM_001167617.3:c.-143_-113dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167618.3:c.-577_-547dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167619.3:c.-485_-455dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258274.3:c.-722_-692dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354615.2:c.-480_-450dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354616.2:c.-485_-455dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354617.2:c.-577_-547dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354618.2:c.-577_-547dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354619.2:c.-577_-547dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354620.2:c.-143_-113dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354621.2:c.-670_-640dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354622.2:c.-783_-753dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354624.2:c.-680_-650dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354625.2:c.-583_-553dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354626.2:c.-680_-650dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354627.2:c.-680_-650dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258273.2:c.-517+2986_-517+3016dup - intron variant - [Sequence Ontology: SO:0001627]
NM_001354623.2:c.-723+2759_-723+2789dup - intron variant - [Sequence Ontology: SO:0001627]
NM_000249.4:c.147_177dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001258271.2:c.147_177dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001354628.2:c.147_177dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001354629.2:c.147_177dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001354630.2:c.147_177dup - nonsense - [Sequence Ontology: SO:0001587]

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
SCV002701278	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (May 3, 2019)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002701278

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(May 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, SCV002701278.2

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

Description

The c.147_177dup31 variant, located in coding exon 2 of the MLH1 gene, results from a duplication of GATTGTTAAAGAGGGAGGCCTGAAGTTGATT at nucleotide position 147, causing a translational frameshift with a predicted alternate stop codon (p.Q60Dfs*3). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. 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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