NM_000179.3(MSH6):c.3679A>T (p.Ile1227Leu) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Sep 12, 2018
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:: RCV000574037.5

Allele description [Variation Report for NM_000179.3(MSH6):c.3679A>T (p.Ile1227Leu)]

NM_000179.3(MSH6):c.3679A>T (p.Ile1227Leu)

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.3679A>T (p.Ile1227Leu)

HGVS:

NC_000002.12:g.47806236A>T
NG_007111.1:g.28090A>T
NG_008397.1:g.104440T>A
NM_000179.3:c.3679A>TMANE SELECT
NM_001281492.2:c.3289A>T
NM_001281493.2:c.2773A>T
NM_001281494.2:c.2773A>T
NP_000170.1:p.Ile1227Leu
NP_000170.1:p.Ile1227Leu
NP_001268421.1:p.Ile1097Leu
NP_001268422.1:p.Ile925Leu
NP_001268423.1:p.Ile925Leu
LRG_219t1:c.3679A>T
LRG_219:g.28090A>T
LRG_219p1:p.Ile1227Leu
NC_000002.11:g.48033375A>T
NM_000179.2:c.3679A>T

Protein change:

I1097L

Links:

dbSNP: rs587779282

NCBI 1000 Genomes Browser:

rs587779282

Molecular consequence:

NM_000179.3:c.3679A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001281492.2:c.3289A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001281493.2:c.2773A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001281494.2:c.2773A>T - missense variant - [Sequence Ontology: SO:0001583]

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

Recent activity

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membrane cofactor protein isoform 6 precursor [Homo sapiens]
membrane cofactor protein isoform 6 precursor [Homo sapiens]
gi|27502411|ref|NP_758863.1|

Protein
Amotl2 angiomotin like 2 [Rattus norvegicus]
Amotl2 angiomotin like 2 [Rattus norvegicus]
Gene ID:65157

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000662547	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Mar 13, 2017)	germline	clinical testing	Citation Link,
SCV000908429	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Sep 12, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000662547

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Mar 13, 2017)

germline

clinical testing

Citation Link,

SCV000908429

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Sep 12, 2018)

germline

clinical testing

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

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

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 Ambry Genetics, SCV000662547.5

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

Description

The p.I1227L variant (also known as c.3679A>T), located in coding exon 8 of the MSH6 gene, results from an A to T substitution at nucleotide position 3679. The isoleucine at codon 1227 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. In addition, the CoDP in silico tool predicts this alteration to have moderate impact on molecular function, with a score of 0.619 (Terui H et al. J. Biomed. Sci. 2013 Apr;20:25). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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 Color Diagnostics, LLC DBA Color Health, SCV000908429.1

#	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

Last Updated: Oct 8, 2024

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