NM_000179.3(MSH6):c.3619_3620del (p.His1207fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 18, 2021
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:: RCV001020737.3

Allele description [Variation Report for NM_000179.3(MSH6):c.3619_3620del (p.His1207fs)]

NM_000179.3(MSH6):c.3619_3620del (p.His1207fs)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

2p16.3

Genomic location:

Preferred name:

NM_000179.3(MSH6):c.3619_3620del (p.His1207fs)

HGVS:

NC_000002.12:g.47805678CA[1]
NC_000002.12:g.47805678_47805679CA[1]
NG_007111.1:g.27532CA[1]
NG_008397.1:g.104995TG[1]
NM_000179.2:c.3619_3620del
NM_000179.3:c.3619_3620delMANE SELECT
NM_001281492.2:c.3229_3230del
NM_001281493.2:c.2713_2714del
NM_001281494.2:c.2713_2714del
NP_000170.1:p.His1207fs
NP_001268421.1:p.His1077fs
NP_001268422.1:p.His905fs
NP_001268423.1:p.His905fs
LRG_219t1:c.3619_3620del
LRG_219:g.27532CA[1]
NC_000002.11:g.48032817CA[1]
NC_000002.11:g.48032817_48032818del
NC_000002.12:g.47805680_47805681delCA
NM_000179.2:c.3619_3620delCA
NM_000179.3:c.3619_3620del

Protein change:

H1077fs

Links:

dbSNP: rs1572741984

NCBI 1000 Genomes Browser:

rs1572741984

Molecular consequence:

NM_000179.3:c.3619_3620del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281492.2:c.3229_3230del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281493.2:c.2713_2714del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281494.2:c.2713_2714del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV001182250	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Mar 18, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26177554, 27601186 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001182250

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Mar 18, 2021)

germline

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

Citations

PubMed

The gynecological surveillance of women with Lynch syndrome in Sweden.

Tzortzatos G, Andersson E, Soller M, Askmalm MS, Zagoras T, Georgii-Hemming P, Lindblom A, Tham E, Mints M.

Gynecol Oncol. 2015 Sep;138(3):717-22. doi: 10.1016/j.ygyno.2015.07.016. Epub 2015 Jul 12.

PubMed [citation]

PMID:: 26177554

Mismatch repair gene mutation spectrum in the Swedish Lynch syndrome population.

Lagerstedt-Robinson K, Rohlin A, Aravidis C, Melin B, Nordling M, Stenmark-Askmalm M, Lindblom A, Nilbert M.

Oncol Rep. 2016 Nov;36(5):2823-2835. doi: 10.3892/or.2016.5060. Epub 2016 Sep 1.

PubMed [citation]

PMID:: 27601186

Details of each submission

From Ambry Genetics, SCV001182250.4

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

Description

The c.3619_3620delCA pathogenic mutation, located in coding exon 7 of the MSH6 gene, results from a deletion of two nucleotides at nucleotide positions 3619 to 3620, causing a translational frameshift with a predicted alternate stop codon (p.H1207Ffs*7). This mutation has been reported in Swedish Lynch syndrome patients (Tzortzatos G et al. Gynecol. Oncol. 2015 Sep;138:717-22; Lagerstedt-Robinson K et al. Oncol. Rep. 2016 Nov;36:2823-2835). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing 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: Jun 23, 2024

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