NM_000249.4(MLH1):c.428_434delinsGG (p.Ala143fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 12, 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:: RCV002330117.2

Allele description [Variation Report for NM_000249.4(MLH1):c.428_434delinsGG (p.Ala143fs)]

NM_000249.4(MLH1):c.428_434delinsGG (p.Ala143fs)

Gene:

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

Variant type:

Indel

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000249.4(MLH1):c.428_434delinsGG (p.Ala143fs)

HGVS:

NC_000003.12:g.37007038_37007044delinsGG
NG_007109.2:g.18689_18695delinsGG
NM_000249.4:c.428_434delinsGGMANE SELECT
NM_001167617.3:c.134_140delinsGG
NM_001167618.3:c.-296_-290delinsGG
NM_001167619.3:c.-204_-198delinsGG
NM_001258271.2:c.428_434delinsGG
NM_001258273.2:c.-296_-290delinsGG
NM_001258274.3:c.-296_-290delinsGG
NM_001354615.2:c.-204_-198delinsGG
NM_001354616.2:c.-204_-198delinsGG
NM_001354617.2:c.-296_-290delinsGG
NM_001354618.2:c.-296_-290delinsGG
NM_001354619.2:c.-296_-290delinsGG
NM_001354620.2:c.134_140delinsGG
NM_001354621.2:c.-389_-383delinsGG
NM_001354622.2:c.-502_-496delinsGG
NM_001354623.2:c.-502_-496delinsGG
NM_001354624.2:c.-399_-393delinsGG
NM_001354625.2:c.-307_-301delinsGG
NM_001354626.2:c.-399_-393delinsGG
NM_001354627.2:c.-399_-393delinsGG
NM_001354628.2:c.428_434delinsGG
NM_001354629.2:c.329_335delinsGG
NM_001354630.2:c.428_434delinsGG
NP_000240.1:p.Ala143Glyfs
NP_000240.1:p.Ala143fs
NP_001161089.1:p.Ala45fs
NP_001245200.1:p.Ala143fs
NP_001341549.1:p.Ala45fs
NP_001341557.1:p.Ala143fs
NP_001341558.1:p.Ala110fs
NP_001341559.1:p.Ala143fs
LRG_216t1:c.428_434delCTGGCAAinsGG
LRG_216:g.18689_18695delinsGG
LRG_216p1:p.Ala143Glyfs
NC_000003.11:g.37048529_37048535delinsGG
NM_000249.3:c.428_434delCTGGCAAinsGG

Protein change:

A110fs

Molecular consequence:

NM_001167618.3:c.-296_-290delinsGG - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167619.3:c.-204_-198delinsGG - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258273.2:c.-296_-290delinsGG - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258274.3:c.-296_-290delinsGG - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354615.2:c.-204_-198delinsGG - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354616.2:c.-204_-198delinsGG - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354617.2:c.-296_-290delinsGG - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354618.2:c.-296_-290delinsGG - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354619.2:c.-296_-290delinsGG - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354621.2:c.-389_-383delinsGG - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354622.2:c.-502_-496delinsGG - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354623.2:c.-502_-496delinsGG - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354624.2:c.-399_-393delinsGG - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354625.2:c.-307_-301delinsGG - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354626.2:c.-399_-393delinsGG - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354627.2:c.-399_-393delinsGG - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000249.4:c.428_434delinsGG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001167617.3:c.134_140delinsGG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258271.2:c.428_434delinsGG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354620.2:c.134_140delinsGG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354628.2:c.428_434delinsGG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354629.2:c.329_335delinsGG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354630.2:c.428_434delinsGG - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV002627853	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Feb 12, 2019)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002627853

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Feb 12, 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, SCV002627853.2

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

Description

The c.428_434delCTGGCAAinsGG pathogenic mutation, located in coding exon 5 of the MLH1 gene, results from the deletion of 7 nucleotides and insertion of two nucleotides causing a translational frameshift with a predicted alternate stop codon (p.A143Gfs*27). 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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