NM_000249.4(MLH1):c.388del (p.Tyr130fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 27, 2018
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:: RCV002354260.2

Allele description [Variation Report for NM_000249.4(MLH1):c.388del (p.Tyr130fs)]

NM_000249.4(MLH1):c.388del (p.Tyr130fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000249.4(MLH1):c.388del (p.Tyr130fs)

HGVS:

NC_000003.12:g.37006998del
NG_007109.2:g.18649del
NM_000249.4:c.388delMANE SELECT
NM_001167617.3:c.94del
NM_001167618.3:c.-336del
NM_001167619.3:c.-244del
NM_001258271.2:c.388del
NM_001258273.2:c.-336del
NM_001258274.3:c.-336del
NM_001354615.2:c.-244del
NM_001354616.2:c.-244del
NM_001354617.2:c.-336del
NM_001354618.2:c.-336del
NM_001354619.2:c.-336del
NM_001354620.2:c.94del
NM_001354621.2:c.-429del
NM_001354622.2:c.-542del
NM_001354623.2:c.-542del
NM_001354624.2:c.-439del
NM_001354625.2:c.-347del
NM_001354626.2:c.-439del
NM_001354627.2:c.-439del
NM_001354628.2:c.388del
NM_001354629.2:c.289del
NM_001354630.2:c.388del
NP_000240.1:p.Tyr130fs
NP_001161089.1:p.Tyr32fs
NP_001245200.1:p.Tyr130fs
NP_001341549.1:p.Tyr32fs
NP_001341557.1:p.Tyr130fs
NP_001341558.1:p.Tyr97fs
NP_001341559.1:p.Tyr130fs
LRG_216t1:c.388del
LRG_216:g.18649del
NC_000003.11:g.37048489del
NM_000249.3:c.388delT

Protein change:

Y130fs

Links:

dbSNP: rs587779009

NCBI 1000 Genomes Browser:

rs587779009

Molecular consequence:

NM_001167618.3:c.-336del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167619.3:c.-244del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258273.2:c.-336del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258274.3:c.-336del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354615.2:c.-244del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354616.2:c.-244del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354617.2:c.-336del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354618.2:c.-336del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354619.2:c.-336del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354621.2:c.-429del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354622.2:c.-542del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354623.2:c.-542del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354624.2:c.-439del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354625.2:c.-347del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354626.2:c.-439del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354627.2:c.-439del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000249.4:c.388del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001167617.3:c.94del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258271.2:c.388del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354620.2:c.94del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354628.2:c.388del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354629.2:c.289del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354630.2:c.388del - 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

Recent activity

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Chain B, POLYMERASE ACIDIC PROTEIN
Chain B, POLYMERASE ACIDIC PROTEIN
gi|582045095|pdb|4CHC|B

Protein
THOV_s3gp1 [Thogoto thogotovirus]
THOV_s3gp1 [Thogoto thogotovirus]
Gene ID:5075734

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002620638	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Sep 27, 2018)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002620638

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Sep 27, 2018)

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, SCV002620638.2

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

Description

The c.388delT pathogenic mutation, located in coding exon 5 of the MLH1 gene, results from a deletion of one nucleotide at nucleotide position 388, causing a translational frameshift with a predicted alternate stop codon (p.Y130Tfs*6). 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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