NM_000179.3(MSH6):c.3922_3938dup (p.Gln1314fs) AND Lynch syndrome 5

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Aug 28, 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:: RCV001258051.2

Allele description [Variation Report for NM_000179.3(MSH6):c.3922_3938dup (p.Gln1314fs)]

NM_000179.3(MSH6):c.3922_3938dup (p.Gln1314fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

2p16.3

Genomic location:

Preferred name:

NM_000179.3(MSH6):c.3922_3938dup (p.Gln1314fs)

HGVS:

NC_000002.12:g.47806572_47806588dup
NG_007111.1:g.28426_28442dup
NG_008397.1:g.104090_104106dup
NM_000179.3:c.3922_3938dupMANE SELECT
NM_001281492.2:c.3532_3548dup
NM_001281493.2:c.3016_3032dup
NM_001281494.2:c.3016_3032dup
NP_000170.1:p.Gln1314fs
NP_001268421.1:p.Gln1184fs
NP_001268422.1:p.Gln1012fs
NP_001268423.1:p.Gln1012fs
LRG_219t1:c.3922_3938dup
LRG_219:g.28426_28442dup
NC_000002.11:g.48033711_48033727dup
NM_000179.2:c.3922_3938dupCTCCCAGAGGAAGTTAT

Protein change:

Q1012fs

Links:

dbSNP: rs1670123011

NCBI 1000 Genomes Browser:

rs1670123011

Molecular consequence:

NM_000179.3:c.3922_3938dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281492.2:c.3532_3548dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281493.2:c.3016_3032dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281494.2:c.3016_3032dup - frameshift variant - [Sequence Ontology: SO:0001589]

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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YLP motif-containing protein 1 isoform 1 [Homo sapiens]
YLP motif-containing protein 1 isoform 1 [Homo sapiens]
gi|146134388|ref|NP_062535.2|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001434881	Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Feb 21, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004188271	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Pathogenic (Aug 28, 2023)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001434881

Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Feb 21, 2019)

germline

clinical testing

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

SCV004188271

Myriad Genetics, Inc.

criteria provided, single submitter

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

Pathogenic
(Aug 28, 2023)

unknown

clinical testing

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
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine, SCV001434881.1

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

Description

The c.3922_3938dup (p.Gln1314Serfs*19) variant in the MSH6 gene is predicted to introduce a premature translational termination codon and has never been observed in general population databases. Therefore, we classify this c.3922_3938dup (p.Gln1314Serfs*19) variant in the MSH6 gene as likely pathogenic.

#	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., SCV004188271.1

#	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 frameshift 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

Last Updated: Oct 8, 2024

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