NM_000249.4(MLH1):c.88_108del (p.Asn30_Ile36del) AND Colorectal cancer, hereditary nonpolyposis, type 2

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jul 10, 2023
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:: RCV003450314.1

Allele description [Variation Report for NM_000249.4(MLH1):c.88_108del (p.Asn30_Ile36del)]

NM_000249.4(MLH1):c.88_108del (p.Asn30_Ile36del)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000249.4(MLH1):c.88_108del (p.Asn30_Ile36del)

HGVS:

NC_000003.12:g.36993635_36993655del
NG_007109.2:g.5286_5306del
NG_008418.1:g.4651_4671del
NG_099042.1:g.28_48del
NG_099042.2:g.164_184del
NM_000249.4:c.88_108delMANE SELECT
NM_001167617.3:c.-429_-409del
NM_001167618.3:c.-858_-838del
NM_001167619.3:c.-771_-751del
NM_001258271.2:c.88_108del
NM_001258273.2:c.-545_-525del
NM_001258274.3:c.-1008_-988del
NM_001354615.2:c.-539_-519del
NM_001354616.2:c.-539_-519del
NM_001354617.2:c.-631_-611del
NM_001354618.2:c.-863_-843del
NM_001354619.2:c.-987_-967del
NM_001354620.2:c.-197_-177del
NM_001354621.2:c.-956_-936del
NM_001354622.2:c.-1069_-1049del
NM_001354623.2:c.-978_-958del
NM_001354624.2:c.-739_-719del
NM_001354625.2:c.-637_-617del
NM_001354626.2:c.-734_-714del
NM_001354627.2:c.-966_-946del
NM_001354628.2:c.88_108del
NM_001354629.2:c.88_108del
NM_001354630.2:c.88_108del
NP_000240.1:p.Asn30_Ile36del
NP_000240.1:p.Asn30_Ile36del
NP_001245200.1:p.Asn30_Ile36del
NP_001341557.1:p.Asn30_Ile36del
NP_001341558.1:p.Asn30_Ile36del
NP_001341559.1:p.Asn30_Ile36del
LRG_216t1:c.88_108del21
LRG_216:g.5286_5306del
LRG_216p1:p.Asn30_Ile36del
NC_000003.11:g.37035126_37035146del
NM_000249.3:c.88_108del21

Molecular consequence:

NM_001167617.3:c.-429_-409del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167618.3:c.-858_-838del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167619.3:c.-771_-751del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258273.2:c.-545_-525del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258274.3:c.-1008_-988del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354615.2:c.-539_-519del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354616.2:c.-539_-519del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354617.2:c.-631_-611del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354618.2:c.-863_-843del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354619.2:c.-987_-967del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354620.2:c.-197_-177del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354621.2:c.-956_-936del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354622.2:c.-1069_-1049del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354623.2:c.-978_-958del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354624.2:c.-739_-719del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354625.2:c.-637_-617del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354626.2:c.-734_-714del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354627.2:c.-966_-946del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000249.4:c.88_108del - inframe deletion - [Sequence Ontology: SO:0001822]
NM_001258271.2:c.88_108del - inframe deletion - [Sequence Ontology: SO:0001822]
NM_001354628.2:c.88_108del - inframe deletion - [Sequence Ontology: SO:0001822]
NM_001354629.2:c.88_108del - inframe deletion - [Sequence Ontology: SO:0001822]
NM_001354630.2:c.88_108del - inframe deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Name:: Colorectal cancer, hereditary nonpolyposis, type 2 (LYNCH2)
Synonyms:: COLON CANCER, FAMILIAL NONPOLYPOSIS, TYPE 2; Lynch syndrome II; MLH1-Related Lynch Syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012249; MedGen: C1333991; Orphanet: 144; OMIM: 609310

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Homo sapiens chromosome 15 genomic patch of type FIX, GRCh38.p14 PATCHES HG2365_PATCH
gi|1595688527|gnl|ASM:GCF_000005045 G2365_PATCH|ref|NW_021160017.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004187113	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Likely pathogenic (Jul 10, 2023)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 10199405, 20864418 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004187113

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))

Likely pathogenic
(Jul 10, 2023)

unknown

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Transformation of MutL by ATP binding and hydrolysis: a switch in DNA mismatch repair.

Ban C, Junop M, Yang W.

Cell. 1999 Apr 2;97(1):85-97.

PubMed [citation]

PMID:: 10199405

Conservation of functional asymmetry in the mammalian MutLα ATPase.

Johnson JR, Erdeniz N, Nguyen M, Dudley S, Liskay RM.

DNA Repair (Amst). 2010 Nov 10;9(11):1209-13. doi: 10.1016/j.dnarep.2010.08.006.

PubMed [citation]

PMID:: 20864418
PMCID:: PMC2970632

Details of each submission

From Myriad Genetics, Inc., SCV004187113.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 10199405, 20864418, Myriad internal data]. This variant is expected to disrupt protein structure [Myriad internal data].

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Dec 30, 2023

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