NM_000179.3(MSH6):c.1444C>T (p.Arg482Ter) AND Lynch syndrome 5

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: May 24, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000410127.3

Allele description [Variation Report for NM_000179.3(MSH6):c.1444C>T (p.Arg482Ter)]

NM_000179.3(MSH6):c.1444C>T (p.Arg482Ter)

Gene:

MSH6:mutS homolog 6 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p16.3

Genomic location:

Preferred name:

NM_000179.3(MSH6):c.1444C>T (p.Arg482Ter)

HGVS:

NC_000002.12:g.47799427C>T
NG_007111.1:g.21281C>T
NM_000179.3:c.1444C>TMANE SELECT
NM_001281492.2:c.1054C>T
NM_001281493.2:c.538C>T
NM_001281494.2:c.538C>T
NP_000170.1:p.Arg482Ter
NP_000170.1:p.Arg482Ter
NP_001268421.1:p.Arg352Ter
NP_001268422.1:p.Arg180Ter
NP_001268423.1:p.Arg180Ter
LRG_219t1:c.1444C>T
LRG_219:g.21281C>T
LRG_219p1:p.Arg482Ter
NC_000002.11:g.48026566C>T
NM_000179.2:c.1444C>T

Protein change:

R180*

Links:

dbSNP: rs63750909

NCBI 1000 Genomes Browser:

rs63750909

Molecular consequence:

NM_000179.3:c.1444C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001281492.2:c.1054C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001281493.2:c.538C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001281494.2:c.538C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Lynch syndrome 5 (LYNCH5)
Synonyms:: Colorectal cancer, hereditary nonpolyposis, type 5; Hereditary non-polyposis colorectal cancer, type 5
Identifiers:: MONDO: MONDO:0013710; MedGen: C1833477; Orphanet: 144; OMIM: 614350

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000489704	Counsyl	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015))	Pathogenic (Nov 9, 2016)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 15236168, 21836479 Counsyl Autosomal Dominant Disease Classification criteria (2015), Citation Link,
SCV004019086	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Pathogenic (Mar 30, 2023)	unknown	clinical testing	Citation Link,
SCV004027792	Institute of Human Genetics, University of Leipzig Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 24, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000489704

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Dominant Disease Classification criteria (2015))

Pathogenic
(Nov 9, 2016)

unknown

clinical testing

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

Counsyl Autosomal Dominant Disease Classification criteria (2015),

Citation Link,

SCV004019086

Myriad Genetics, Inc.

criteria provided, single submitter

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

Pathogenic
(Mar 30, 2023)

unknown

clinical testing

Citation Link,

SCV004027792

Institute of Human Genetics, University of Leipzig Medical Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 24, 2023)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Cancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations: impact on counseling and surveillance.

Hendriks YM, Wagner A, Morreau H, Menko F, Stormorken A, Quehenberger F, Sandkuijl L, Møller P, Genuardi M, Van Houwelingen H, Tops C, Van Puijenbroek M, Verkuijlen P, Kenter G, Van Mil A, Meijers-Heijboer H, Tan GB, Breuning MH, Fodde R, Wijnen JT, Bröcker-Vriends AH, Vasen H.

Gastroenterology. 2004 Jul;127(1):17-25.

PubMed [citation]

PMID:: 15236168

Challenges in the identification of MSH6-associated colorectal cancer: rectal location, less typical histology, and a subset with retained mismatch repair function.

Klarskov L, Holck S, Bernstein I, Okkels H, Rambech E, Baldetorp B, Nilbert M.

Am J Surg Pathol. 2011 Sep;35(9):1391-9. doi: 10.1097/PAS.0b013e318225c3f0.

PubMed [citation]

PMID:: 21836479

See all PubMed Citations (3)

Details of each submission

From Counsyl, SCV000489704.2

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

#	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

From Myriad Genetics, Inc., SCV004019086.1

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

Description

This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.

#	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

From Institute of Human Genetics, University of Leipzig Medical Center, SCV004027792.1

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

Description

Criteria applied: PVS1,PS4_MOD,PM2_SUP

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

Last Updated: Nov 10, 2024

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