NM_000249.4(MLH1):c.191dup (p.Asn64fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 18, 2024
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:: RCV004019102.1

Allele description [Variation Report for NM_000249.4(MLH1):c.191dup (p.Asn64fs)]

NM_000249.4(MLH1):c.191dup (p.Asn64fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000249.4(MLH1):c.191dup (p.Asn64fs)

HGVS:

NC_000003.12:g.36996693dup
NG_007109.2:g.8344dup
NG_008418.1:g.1613dup
NM_000249.3:c.191dupA
NM_000249.4:c.191dupMANE SELECT
NM_001167617.3:c.-99dup
NM_001167618.3:c.-533dup
NM_001167619.3:c.-441dup
NM_001258271.2:c.191dup
NM_001258273.2:c.-517+3030dup
NM_001258274.3:c.-678dup
NM_001354615.2:c.-436dup
NM_001354616.2:c.-441dup
NM_001354617.2:c.-533dup
NM_001354618.2:c.-533dup
NM_001354619.2:c.-533dup
NM_001354620.2:c.-99dup
NM_001354621.2:c.-626dup
NM_001354622.2:c.-739dup
NM_001354623.2:c.-723+2803dup
NM_001354624.2:c.-636dup
NM_001354625.2:c.-539dup
NM_001354626.2:c.-636dup
NM_001354627.2:c.-636dup
NM_001354628.2:c.191dup
NM_001354629.2:c.191dup
NM_001354630.2:c.191dup
NP_000240.1:p.Asn64fs
NP_001245200.1:p.Asn64fs
NP_001341557.1:p.Asn64fs
NP_001341558.1:p.Asn64fs
NP_001341559.1:p.Asn64fs
LRG_216t1:c.191dup
LRG_216:g.8344dup
NC_000003.11:g.37038184dup

Protein change:

N64fs

Links:

dbSNP: rs63751255

NCBI 1000 Genomes Browser:

rs63751255

Molecular consequence:

NM_001167617.3:c.-99dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167618.3:c.-533dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167619.3:c.-441dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258274.3:c.-678dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354615.2:c.-436dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354616.2:c.-441dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354617.2:c.-533dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354618.2:c.-533dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354619.2:c.-533dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354620.2:c.-99dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354621.2:c.-626dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354622.2:c.-739dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354624.2:c.-636dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354625.2:c.-539dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354626.2:c.-636dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354627.2:c.-636dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000249.4:c.191dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258271.2:c.191dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354628.2:c.191dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354629.2:c.191dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354630.2:c.191dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258273.2:c.-517+3030dup - intron variant - [Sequence Ontology: SO:0001627]
NM_001354623.2:c.-723+2803dup - intron variant - [Sequence Ontology: SO:0001627]

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
SCV005033255	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jan 18, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005033255

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jan 18, 2024)

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, SCV005033255.1

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

Description

The c.191dupA pathogenic mutation, located in coding exon 2 of the MLH1 gene, results from a duplication of A at nucleotide position 191, causing a translational frameshift with a predicted alternate stop codon (p.N64Kfs*15). 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 7, 2024

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