NM_000179.3(MSH6):c.124C>T (p.Pro42Ser) AND Lynch syndrome 5

Germline classification:: Conflicting classifications of pathogenicity (4 submissions)
Last evaluated:: Mar 30, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV000410444.8

Allele description [Variation Report for NM_000179.3(MSH6):c.124C>T (p.Pro42Ser)]

NM_000179.3(MSH6):c.124C>T (p.Pro42Ser)

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.124C>T (p.Pro42Ser)

HGVS:

NC_000002.12:g.47783357C>T
NG_007111.1:g.5211C>T
NM_000179.3:c.124C>TMANE SELECT
NM_001281492.2:c.124C>T
NM_001281493.2:c.-613C>T
NP_000170.1:p.Pro42Ser
NP_000170.1:p.Pro42Ser
NP_001268421.1:p.Pro42Ser
LRG_219t1:c.124C>T
LRG_219:g.5211C>T
LRG_219p1:p.Pro42Ser
NC_000002.11:g.48010496C>T
NM_000179.2:c.124C>T
p.P42S

Protein change:

P42S

Links:

dbSNP: rs34014629

NCBI 1000 Genomes Browser:

rs34014629

Molecular consequence:

NM_001281493.2:c.-613C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000179.3:c.124C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001281492.2:c.124C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000488256	Counsyl	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015))	Uncertain significance (Feb 9, 2016)	unknown	clinical testing	PubMed (6) [See all records that cite these PMIDs] 26437257, 15872200, 25980754, 21153778, 22290698, 23621914 Counsyl Autosomal Dominant Disease Classification criteria (2015), Citation Link,
SCV001135775	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Likely benign (May 28, 2019)	unknown	clinical testing	Citation Link,
SCV002570276	Johns Hopkins Genomics, Johns Hopkins University	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Mar 19, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 20301390, 22290698, 25980754, 31647837, 25741868
SCV004019091	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Benign (Mar 30, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] 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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical and Molecular Characterization of Brazilian Patients Suspected to Have Lynch Syndrome.

Carneiro da Silva F, Ferreira JR, Torrezan GT, Figueiredo MC, Santos ÉM, Nakagawa WT, Brianese RC, Petrolini de Oliveira L, Begnani MD, Aguiar-Junior S, Rossi BM, Ferreira Fde O, Carraro DM.

PLoS One. 2015;10(10):e0139753. doi: 10.1371/journal.pone.0139753.

PubMed [citation]

PMID:: 26437257
PMCID:: PMC4593564

Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer).

Hampel H, Frankel WL, Martin E, Arnold M, Khanduja K, Kuebler P, Nakagawa H, Sotamaa K, Prior TW, Westman J, Panescu J, Fix D, Lockman J, Comeras I, de la Chapelle A.

N Engl J Med. 2005 May 5;352(18):1851-60.

PubMed [citation]

PMID:: 15872200

See all PubMed Citations (10)

Details of each submission

From Counsyl, SCV000488256.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

#	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 Mendelics, SCV001135775.1

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

#	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 Johns Hopkins Genomics, Johns Hopkins University, SCV002570276.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

#	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

From Myriad Genetics, Inc., SCV004019091.1

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

Description

This variant is considered benign. Homozygosity for this variant has been confirmed in one or more individuals lacking clinical features consistent with gene-specific recessive disease, indicating that this variant is unlikely to be pathogenic. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752].

#	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: Jan 19, 2025

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