NM_000249.4(MLH1):c.129_133del (p.Lys43fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 21, 2020
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:: RCV002383293.2

Allele description [Variation Report for NM_000249.4(MLH1):c.129_133del (p.Lys43fs)]

NM_000249.4(MLH1):c.129_133del (p.Lys43fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000249.4(MLH1):c.129_133del (p.Lys43fs)

HGVS:

NC_000003.12:g.36996631_36996635del
NG_007109.2:g.8282_8286del
NG_008418.1:g.1671_1675del
NM_000249.4:c.129_133delMANE SELECT
NM_001167617.3:c.-161_-157del
NM_001167618.3:c.-595_-591del
NM_001167619.3:c.-503_-499del
NM_001258271.2:c.129_133del
NM_001258273.2:c.-517+2968_-517+2972del
NM_001258274.3:c.-740_-736del
NM_001354615.2:c.-498_-494del
NM_001354616.2:c.-503_-499del
NM_001354617.2:c.-595_-591del
NM_001354618.2:c.-595_-591del
NM_001354619.2:c.-595_-591del
NM_001354620.2:c.-161_-157del
NM_001354621.2:c.-688_-684del
NM_001354622.2:c.-801_-797del
NM_001354623.2:c.-723+2741_-723+2745del
NM_001354624.2:c.-698_-694del
NM_001354625.2:c.-601_-597del
NM_001354626.2:c.-698_-694del
NM_001354627.2:c.-698_-694del
NM_001354628.2:c.129_133del
NM_001354629.2:c.129_133del
NM_001354630.2:c.129_133del
NP_000240.1:p.Lys43Asnfs
NP_000240.1:p.Lys43fs
NP_001245200.1:p.Lys43fs
NP_001341557.1:p.Lys43fs
NP_001341558.1:p.Lys43fs
NP_001341559.1:p.Lys43fs
LRG_216t1:c.129_133del
LRG_216:g.8282_8286del
LRG_216p1:p.Lys43Asnfs
NC_000003.11:g.37038122_37038126del
NM_000249.3:c.129_133delATCCA

Protein change:

K43fs

Molecular consequence:

NM_001167617.3:c.-161_-157del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167618.3:c.-595_-591del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167619.3:c.-503_-499del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258274.3:c.-740_-736del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354615.2:c.-498_-494del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354616.2:c.-503_-499del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354617.2:c.-595_-591del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354618.2:c.-595_-591del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354619.2:c.-595_-591del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354620.2:c.-161_-157del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354621.2:c.-688_-684del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354622.2:c.-801_-797del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354624.2:c.-698_-694del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354625.2:c.-601_-597del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354626.2:c.-698_-694del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354627.2:c.-698_-694del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000249.4:c.129_133del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258271.2:c.129_133del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354628.2:c.129_133del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354629.2:c.129_133del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354630.2:c.129_133del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258273.2:c.-517+2968_-517+2972del - intron variant - [Sequence Ontology: SO:0001627]
NM_001354623.2:c.-723+2741_-723+2745del - 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
SCV002691639	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Dec 21, 2020)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002691639

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Dec 21, 2020)

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, SCV002691639.2

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

Description

The c.129_133delATCCA pathogenic mutation, located in coding exon 2 of the MLH1 gene, results from a deletion of 5 nucleotides at nucleotide positions 129 to 133, causing a translational frameshift with a predicted alternate stop codon (p.K43Nfs*8). 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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