NM_000249.4(MLH1):c.36_38del (p.Asp12del) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 3, 2014
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:: RCV002455199.2

Allele description [Variation Report for NM_000249.4(MLH1):c.36_38del (p.Asp12del)]

NM_000249.4(MLH1):c.36_38del (p.Asp12del)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000249.4(MLH1):c.36_38del (p.Asp12del)

HGVS:

NC_000003.12:g.36993583_36993585del
NG_007109.2:g.5234_5236del
NG_008418.1:g.4722_4724del
NM_000249.4:c.36_38delMANE SELECT
NM_001167617.3:c.-481_-479del
NM_001167618.3:c.-910_-908del
NM_001167619.3:c.-823_-821del
NM_001258271.2:c.36_38del
NM_001258273.2:c.-597_-595del
NM_001258274.3:c.-1060_-1058del
NM_001354615.2:c.-591_-589del
NM_001354616.2:c.-591_-589del
NM_001354617.2:c.-683_-681del
NM_001354618.2:c.-915_-913del
NM_001354619.2:c.-1039_-1037del
NM_001354620.2:c.-249_-247del
NM_001354621.2:c.-1008_-1006del
NM_001354622.2:c.-1121_-1119del
NM_001354623.2:c.-1030_-1028del
NM_001354624.2:c.-791_-789del
NM_001354625.2:c.-689_-687del
NM_001354626.2:c.-786_-784del
NM_001354627.2:c.-1018_-1016del
NM_001354628.2:c.36_38del
NM_001354629.2:c.36_38del
NM_001354630.2:c.36_38del
NP_000240.1:p.Asp12del
NP_000240.1:p.Asp12del
NP_001245200.1:p.Asp12del
NP_001341557.1:p.Asp12del
NP_001341558.1:p.Asp12del
NP_001341559.1:p.Asp12del
LRG_216t1:c.36_38del
LRG_216:g.5234_5236del
LRG_216p1:p.Asp12del
NC_000003.11:g.37035074_37035076del
NM_000249.3:c.36_38delCGA

Protein change:

D12del

Molecular consequence:

NM_001167617.3:c.-481_-479del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167618.3:c.-910_-908del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167619.3:c.-823_-821del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258273.2:c.-597_-595del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258274.3:c.-1060_-1058del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354615.2:c.-591_-589del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354616.2:c.-591_-589del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354617.2:c.-683_-681del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354618.2:c.-915_-913del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354619.2:c.-1039_-1037del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354620.2:c.-249_-247del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354621.2:c.-1008_-1006del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354622.2:c.-1121_-1119del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354623.2:c.-1030_-1028del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354624.2:c.-791_-789del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354625.2:c.-689_-687del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354626.2:c.-786_-784del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354627.2:c.-1018_-1016del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000249.4:c.36_38del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001258271.2:c.36_38del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001354628.2:c.36_38del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001354629.2:c.36_38del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001354630.2:c.36_38del - inframe_deletion - [Sequence Ontology: SO:0001822]

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
SCV002614946	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Oct 3, 2014)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002614946

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Oct 3, 2014)

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, SCV002614946.2

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

Description

The c.36_38delCGA pathogenic mutation (also known as p.D12del) is located in coding exon 1 of the MLH1 gene. This variant results from a deletion of three nucleotides at positions 36-38 and the removal of a highly conserved aspartate residue at codon 12. This mutation has been determined to be the result of a de novo event in one family with an isolated case of early onset colon cancer. This variant was not reported in population-based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project. Based on the available evidence, c.36_38delCGA is classified as a pathogenic 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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