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NM_000179.2(MSH6):c.2561_2562delinsTT (p.Lys854Ile)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(2);Uncertain significance(3)

Review status:
criteria provided, conflicting interpretations
Submissions:
6 (Most recent: Jun 11, 2021)
Last evaluated:
Jul 15, 2020
Accession:
VCV000135836.11
Variation ID:
135836
Description:
2bp indel
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NM_000179.2(MSH6):c.2561_2562delinsTT (p.Lys854Ile)

Allele ID
139548
Variant type
Indel
Variant length
2 bp
Cytogenetic location
2p16.3
Genomic location
2: 47800544-47800545 (GRCh38) GRCh38 UCSC
2: 48027683-48027684 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000002.11:g.48027683_48027684delinsTT
NC_000002.12:g.47800544_47800545delinsTT
NM_000179.2:c.2561_2562delinsTT NP_000170.1:p.Lys854Ile missense
... more HGVS
Protein change
K552I, K724I, K854I
Other names
-
Canonical SPDI
NC_000002.12:47800543:AG:TT
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA010405
dbSNP: rs587780673
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 2 criteria provided, multiple submitters, no conflicts Jul 15, 2020 RCV000214497.7
Likely benign 1 criteria provided, single submitter Mar 26, 2019 RCV000122958.7
Uncertain significance 1 criteria provided, single submitter May 17, 2019 RCV001193127.1
Likely benign 1 criteria provided, single submitter Apr 2, 2020 RCV001284519.1
Uncertain significance 1 no assertion criteria provided - RCV001355264.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
MSH6 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
5637 5671

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(May 17, 2019)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001361764.1
Submitted: (Mar 06, 2020)
Evidence details
Publications
PubMed (1)
Comment:
Variant summary: MSH6 c.2561_2562delinsTT (p.Lys854Ile) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging … (more)
Uncertain significance
(Jul 15, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000273126.6
Submitted: (Nov 30, 2020)
Evidence details
Comment:
The c.2561_2562delAGinsTT variant (also known as p.K854I), located in coding exon 4 of the MSH6 gene, results from an in-frame deletion of AG and insertion … (more)
Likely benign
(Mar 26, 2019)
criteria provided, single submitter
Method: clinical testing
Hereditary nonpolyposis colorectal neoplasms
Allele origin: germline
Invitae
Accession: SCV000166222.8
Submitted: (Jan 07, 2021)
Evidence details
Uncertain significance
(Jun 08, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV000685295.4
Submitted: (Jun 11, 2021)
Evidence details
Comment:
This missense variant replaces lysine with isoleucine at codon 854 of the MSH6 protein. Computational prediction suggests that this variant may have deleterious impact on … (more)
Likely benign
(Apr 02, 2020)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: unknown
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV001470354.1
Submitted: (Dec 31, 2020)
Evidence details
Uncertain significance
(-)
no assertion criteria provided
Method: clinical testing
Malignant tumor of breast
Allele origin: unknown
Department of Pathology and Laboratory Medicine,Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001550095.1
Submitted: (Mar 31, 2021)
Evidence details
Comment:
The MSH6 p.Lys854Ile variant was identified in 2 of 80 proband chromosomes (frequency: 0.03) from individuals or families with breast cancer (Zick 2015). The variant … (more)

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Assigning clinical meaning to somatic and germ-line whole-exome sequencing data in a prospective cancer precision medicine study. Ghazani AA Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28125075

Text-mined citations for rs587780673...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Aug 11, 2021