NM_000179.3(MSH6):c.2300C>G (p.Thr767Ser) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Nov 22, 2022
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:: RCV001284514.10

Allele description [Variation Report for NM_000179.3(MSH6):c.2300C>G (p.Thr767Ser)]

NM_000179.3(MSH6):c.2300C>G (p.Thr767Ser)

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.2300C>G (p.Thr767Ser)

HGVS:

NC_000002.12:g.47800283C>G
NG_007111.1:g.22137C>G
NM_000179.3:c.2300C>GMANE SELECT
NM_001281492.2:c.1910C>G
NM_001281493.2:c.1394C>G
NM_001281494.2:c.1394C>G
NP_000170.1:p.Thr767Ser
NP_000170.1:p.Thr767Ser
NP_001268421.1:p.Thr637Ser
NP_001268422.1:p.Thr465Ser
NP_001268423.1:p.Thr465Ser
LRG_219t1:c.2300C>G
LRG_219:g.22137C>G
LRG_219p1:p.Thr767Ser
NC_000002.11:g.48027422C>G
NM_000179.2:c.2300C>G

Protein change:

T465S

Links:

dbSNP: rs587781462

NCBI 1000 Genomes Browser:

rs587781462

Molecular consequence:

NM_000179.3:c.2300C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281492.2:c.1910C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281493.2:c.1394C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281494.2:c.1394C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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PREDICTED: Ciona intestinalis guanine nucleotide-binding protein G(I)/G(S)/G(T) ...
PREDICTED: Ciona intestinalis guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (LOC100182745), mRNA
gi|1494806935|ref|XM_002127260.5|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000566848	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Nov 8, 2022)	germline	clinical testing	Citation Link,
SCV001470347	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Nov 22, 2022)	unknown	clinical testing	PubMed (5) [See all records that cite these PMIDs] 33471991, 29212164, 25892863, 31100584, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000566848

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Nov 8, 2022)

germline

clinical testing

Citation Link,

SCV001470347

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Nov 22, 2022)

unknown

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

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

Citations

PubMed

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

Targeted sequencing of established and candidate colorectal cancer genes in the Colon Cancer Family Registry Cohort.

Raskin L, Guo Y, Du L, Clendenning M, Rosty C; Colon Cancer Family Registry (CCFR)., Lindor NM, Gruber SB, Buchanan DD.

Oncotarget. 2017 Nov 7;8(55):93450-93463. doi: 10.18632/oncotarget.18596.

PubMed [citation]

PMID:: 29212164
PMCID:: PMC5706810

See all PubMed Citations (5)

Details of each submission

From GeneDx, SCV000566848.3

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

Description

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27601186, 25892863, 27093186, 25010007, 17531815, 21120944, 29212164)

#	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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV001470347.2

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

Description

The frequency of this variant in the general population, 0.00022 (4/18394 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 ((PMID: 25892863 (2015), 29212164 (2017)). The variant has also been reported to occur with an MLH1 truncating variant in a family with colorectal cancer (PMID: 25892863 (2015)). In a large-scale breast cancer association study, the variant was observed in an individual with breast cancer as well as in unaffected individuals (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

Last Updated: Oct 26, 2024

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