NM_000179.3(MSH6):c.2473A>C (p.Ile825Leu) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 2, 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:: RCV002450622.2

Allele description [Variation Report for NM_000179.3(MSH6):c.2473A>C (p.Ile825Leu)]

NM_000179.3(MSH6):c.2473A>C (p.Ile825Leu)

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.2473A>C (p.Ile825Leu)

HGVS:

NC_000002.12:g.47800456A>C
NG_007111.1:g.22310A>C
NM_000179.3:c.2473A>CMANE SELECT
NM_001281492.2:c.2083A>C
NM_001281493.2:c.1567A>C
NM_001281494.2:c.1567A>C
NM_001406795.1:c.2569A>C
NM_001406796.1:c.2473A>C
NM_001406797.1:c.2176A>C
NM_001406798.1:c.2473A>C
NM_001406799.1:c.1948A>C
NM_001406800.1:c.2473A>C
NM_001406801.1:c.2176A>C
NM_001406802.1:c.2569A>C
NM_001406804.1:c.2395A>C
NM_001406805.1:c.2176A>C
NM_001406806.1:c.1948A>C
NM_001406807.1:c.1948A>C
NM_001406808.1:c.2473A>C
NM_001406809.1:c.2473A>C
NM_001406811.1:c.1567A>C
NM_001406812.1:c.1567A>C
NM_001406813.1:c.2479A>C
NM_001406814.1:c.1567A>C
NM_001406815.1:c.1567A>C
NM_001406816.1:c.1567A>C
NM_001406818.1:c.2176A>C
NM_001406819.1:c.2176A>C
NM_001406820.1:c.2176A>C
NM_001406821.1:c.2176A>C
NM_001406822.1:c.2176A>C
NM_001406823.1:c.1567A>C
NM_001406824.1:c.2176A>C
NM_001406825.1:c.2176A>C
NM_001406826.1:c.2305A>C
NM_001406827.1:c.2176A>C
NM_001406828.1:c.2176A>C
NM_001406829.1:c.1567A>C
NM_001406830.1:c.2176A>C
NP_000170.1:p.Ile825Leu
NP_000170.1:p.Ile825Leu
NP_001268421.1:p.Ile695Leu
NP_001268422.1:p.Ile523Leu
NP_001268423.1:p.Ile523Leu
NP_001393724.1:p.Ile857Leu
NP_001393725.1:p.Ile825Leu
NP_001393726.1:p.Ile726Leu
NP_001393727.1:p.Ile825Leu
NP_001393728.1:p.Ile650Leu
NP_001393729.1:p.Ile825Leu
NP_001393730.1:p.Ile726Leu
NP_001393731.1:p.Ile857Leu
NP_001393733.1:p.Ile799Leu
NP_001393734.1:p.Ile726Leu
NP_001393735.1:p.Ile650Leu
NP_001393736.1:p.Ile650Leu
NP_001393737.1:p.Ile825Leu
NP_001393738.1:p.Ile825Leu
NP_001393740.1:p.Ile523Leu
NP_001393741.1:p.Ile523Leu
NP_001393742.1:p.Ile827Leu
NP_001393743.1:p.Ile523Leu
NP_001393744.1:p.Ile523Leu
NP_001393745.1:p.Ile523Leu
NP_001393747.1:p.Ile726Leu
NP_001393748.1:p.Ile726Leu
NP_001393749.1:p.Ile726Leu
NP_001393750.1:p.Ile726Leu
NP_001393751.1:p.Ile726Leu
NP_001393752.1:p.Ile523Leu
NP_001393753.1:p.Ile726Leu
NP_001393754.1:p.Ile726Leu
NP_001393755.1:p.Ile769Leu
NP_001393756.1:p.Ile726Leu
NP_001393757.1:p.Ile726Leu
NP_001393758.1:p.Ile523Leu
NP_001393759.1:p.Ile726Leu
LRG_219t1:c.2473A>C
LRG_219:g.22310A>C
LRG_219p1:p.Ile825Leu
NC_000002.11:g.48027595A>C
NM_000179.2:c.2473A>C
NR_176256.1:n.1335A>C
NR_176257.1:n.2562A>C
NR_176258.1:n.2562A>C
NR_176259.1:n.2562A>C
NR_176261.1:n.2562A>C

Protein change:

I523L

Molecular consequence:

NM_000179.3:c.2473A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001281492.2:c.2083A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001281493.2:c.1567A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001281494.2:c.1567A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406795.1:c.2569A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406796.1:c.2473A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406797.1:c.2176A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406798.1:c.2473A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406799.1:c.1948A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406800.1:c.2473A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406801.1:c.2176A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406802.1:c.2569A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406804.1:c.2395A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406805.1:c.2176A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406806.1:c.1948A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406807.1:c.1948A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406808.1:c.2473A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406809.1:c.2473A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406811.1:c.1567A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406812.1:c.1567A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406813.1:c.2479A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406814.1:c.1567A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406815.1:c.1567A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406816.1:c.1567A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406818.1:c.2176A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406819.1:c.2176A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406820.1:c.2176A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406821.1:c.2176A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406822.1:c.2176A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406823.1:c.1567A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406824.1:c.2176A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406825.1:c.2176A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406826.1:c.2305A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406827.1:c.2176A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406828.1:c.2176A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406829.1:c.1567A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406830.1:c.2176A>C - 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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Homo sapiens GDNF family receptor alpha 4 (GFRA4), transcript variant 1, mRNA
Homo sapiens GDNF family receptor alpha 4 (GFRA4), transcript variant 1, mRNA
gi|1843978348|ref|NM_022139.4|

Nucleotide
Corynebacterium sp. SFY-M4
Corynebacterium sp. SFY-M4
Corynebacterium sp. SFY-M4 Genome sequencing and assembly

BioProject
PREDICTED: Cyclopterus lumpus laminin, alpha 1 (lama1), mRNA
PREDICTED: Cyclopterus lumpus laminin, alpha 1 (lama1), mRNA
gi|1842280805|ref|XM_034560689.1|

Nucleotide
PREDICTED: Mus caroli olfactory receptor 12D3 (LOC110284293), mRNA
PREDICTED: Mus caroli olfactory receptor 12D3 (LOC110284293), mRNA
gi|1195698457|ref|XM_021150012.1|

Nucleotide
cytochrome c oxidase subunit II, partial (mitochondrion) [Zenonoida eltola]
cytochrome c oxidase subunit II, partial (mitochondrion) [Zenonoida eltola]
gi|1376273144|gb|AVX45352.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002735609	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Nov 2, 2021)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002735609

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Nov 2, 2021)

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

Details of each submission

From Ambry Genetics, SCV002735609.2

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

Description

The p.I825L variant (also known as c.2473A>C), located in coding exon 4 of the MSH6 gene, results from an A to C substitution at nucleotide position 2473. The isoleucine at codon 825 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. 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

Last Updated: May 1, 2024

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