NM_000179.3(MSH6):c.2006T>C (p.Ile669Thr) AND not provided

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: May 17, 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:: RCV000679222.11

Allele description [Variation Report for NM_000179.3(MSH6):c.2006T>C (p.Ile669Thr)]

NM_000179.3(MSH6):c.2006T>C (p.Ile669Thr)

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.2006T>C (p.Ile669Thr)

HGVS:

NC_000002.12:g.47799989T>C
NG_007111.1:g.21843T>C
NM_000179.3:c.2006T>CMANE SELECT
NM_001281492.2:c.1616T>C
NM_001281493.2:c.1100T>C
NM_001281494.2:c.1100T>C
NP_000170.1:p.Ile669Thr
NP_000170.1:p.Ile669Thr
NP_001268421.1:p.Ile539Thr
NP_001268422.1:p.Ile367Thr
NP_001268423.1:p.Ile367Thr
LRG_219t1:c.2006T>C
LRG_219:g.21843T>C
LRG_219p1:p.Ile669Thr
NC_000002.11:g.48027128T>C
NM_000179.2:c.2006T>C
p.I669T

Protein change:

I367T

Links:

dbSNP: rs555209664

NCBI 1000 Genomes Browser:

rs555209664

Molecular consequence:

NM_000179.3:c.2006T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001281492.2:c.1616T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001281493.2:c.1100T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001281494.2:c.1100T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

PREDICTED: Mus musculus forkhead box P1 (Foxp1), transcript variant X31, mRNA
PREDICTED: Mus musculus forkhead box P1 (Foxp1), transcript variant X31, mRNA
gi|1907169791|ref|XM_030255068.2|

Nucleotide
Homo sapiens zinc finger MYND-type containing 11 (ZMYND11), transcript variant 1...
Homo sapiens zinc finger MYND-type containing 11 (ZMYND11), transcript variant 18, mRNA
gi|1779859782|ref|NM_001370105.2|

Nucleotide
Human DNA sequence from clone RP11-93H24 on chromosome 13, complete sequence
Human DNA sequence from clone RP11-93H24 on chromosome 13, complete sequence
gi|14148776|emb|AL139089.13|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000601525	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (May 10, 2023)	unknown	clinical testing	PubMed (8) [See all records that cite these PMIDs] 29575718, 33471991, 31927803, 28932927, 31391288, 22290698, 23621914, 26467025
SCV000805855	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 31, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001791272	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (May 17, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000601525

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(May 10, 2023)

unknown

clinical testing

PubMed (8)
[See all records that cite these PMIDs]

SCV000805855

PreventionGenetics, part of Exact Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 31, 2017)

germline

clinical testing

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

SCV001791272

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(May 17, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Germline MLH1, MSH2 and MSH6 variants in Brazilian patients with colorectal cancer and clinical features suggestive of Lynch Syndrome.

Schneider NB, Pastor T, Paula AE, Achatz MI, Santos ÂRD, Vianna FSL, Rosset C, Pinheiro M, Ashton-Prolla P, Moreira MÂM, Palmero EI; Brazilian Lynch Syndrome Study Group..

Cancer Med. 2018 May;7(5):2078-2088. doi: 10.1002/cam4.1316. Epub 2018 Mar 25.

PubMed [citation]

PMID:: 29575718
PMCID:: PMC5943474

Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women.

Breast Cancer Association Consortium., Dorling L, Carvalho S, Allen J, González-Neira A, Luccarini C, Wahlström C, Pooley KA, Parsons MT, Fortuno C, Wang Q, Bolla MK, Dennis J, Keeman R, Alonso MR, Álvarez N, Herraez B, Fernandez V, Núñez-Torres R, Osorio A, Valcich J, Li M, et al.

N Engl J Med. 2021 Feb 4;384(5):428-439. doi: 10.1056/NEJMoa1913948. Epub 2021 Jan 20.

PubMed [citation]

PMID:: 33471991
PMCID:: PMC7611105

See all PubMed Citations (9)

Details of each submission

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000601525.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

The frequency of this variant in the general population, 0.00017 (6/34582 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in individuals with colorectal cancer (CRC) (PMIDs: 29575718 (2018), 31927803 (2020)), Lynch syndrome (PMID: 28932927 (2018)), and unspecified cancers (PMID: 31391288 (2020)). It has also been reported in individuals with breast cancer as well as in unaffected controls in a breast cancer association study (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/MSH6)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant.

#	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 PreventionGenetics, part of Exact Sciences, SCV000805855.1

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

#	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 GeneDx, SCV001791272.2

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

Description

In silico analysis supports that this missense variant does not alter protein structure/function; Observed in individuals with colorectal or other cancers (Soares et al., 2017; Schneider et al., 2018; Greenberg et al., 2020; Li et al., 2020); This variant is associated with the following publications: (PMID: 23621914, 28932927, 26333163, 29575718, 31927803, 17531815, 21120944, 22290698, 31391288)

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

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine