NM_000179.3(MSH6):c.4033G>T (p.Val1345Leu) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 30, 2015
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:: RCV002321180.2

Allele description [Variation Report for NM_000179.3(MSH6):c.4033G>T (p.Val1345Leu)]

NM_000179.3(MSH6):c.4033G>T (p.Val1345Leu)

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.4033G>T (p.Val1345Leu)

HGVS:

NC_000002.12:g.47806810G>T
NG_007111.1:g.28664G>T
NG_008397.1:g.103866C>A
NM_000179.3:c.4033G>TMANE SELECT
NM_001281492.2:c.3643G>T
NM_001281493.2:c.3127G>T
NM_001281494.2:c.3127G>T
NM_001406795.1:c.4129G>T
NM_001406796.1:c.4033G>T
NM_001406797.1:c.3736G>T
NM_001406798.1:c.3859G>T
NM_001406799.1:c.3508G>T
NM_001406800.1:c.*54G>T
NM_001406801.1:c.*14G>T
NM_001406802.1:c.*14G>T
NM_001406803.1:c.3169G>T
NM_001406804.1:c.3955G>T
NM_001406805.1:c.3736G>T
NM_001406806.1:c.3508G>T
NM_001406807.1:c.3508G>T
NM_001406808.1:c.*14G>T
NM_001406809.1:c.4033G>T
NM_001406811.1:c.3127G>T
NM_001406812.1:c.3127G>T
NM_001406813.1:c.4039G>T
NM_001406814.1:c.3127G>T
NM_001406815.1:c.3127G>T
NM_001406816.1:c.3127G>T
NM_001406817.1:c.2467G>T
NM_001406818.1:c.3736G>T
NM_001406819.1:c.3736G>T
NM_001406820.1:c.3736G>T
NM_001406821.1:c.3736G>T
NM_001406822.1:c.*14G>T
NM_001406823.1:c.3127G>T
NM_001406824.1:c.3736G>T
NM_001406825.1:c.3736G>T
NM_001406826.1:c.3865G>T
NM_001406827.1:c.3736G>T
NM_001406828.1:c.3736G>T
NM_001406829.1:c.3127G>T
NM_001406830.1:c.3736G>T
NM_001406831.1:c.814G>T
NM_001406832.1:c.880G>T
NM_001407362.1:c.1978G>T
NP_000170.1:p.Val1345Leu
NP_000170.1:p.Val1345Leu
NP_001268421.1:p.Val1215Leu
NP_001268422.1:p.Val1043Leu
NP_001268423.1:p.Val1043Leu
NP_001393724.1:p.Val1377Leu
NP_001393725.1:p.Val1345Leu
NP_001393726.1:p.Val1246Leu
NP_001393727.1:p.Val1287Leu
NP_001393728.1:p.Val1170Leu
NP_001393732.1:p.Val1057Leu
NP_001393733.1:p.Val1319Leu
NP_001393734.1:p.Val1246Leu
NP_001393735.1:p.Val1170Leu
NP_001393736.1:p.Val1170Leu
NP_001393738.1:p.Val1345Leu
NP_001393740.1:p.Val1043Leu
NP_001393741.1:p.Val1043Leu
NP_001393742.1:p.Val1347Leu
NP_001393743.1:p.Val1043Leu
NP_001393744.1:p.Val1043Leu
NP_001393745.1:p.Val1043Leu
NP_001393746.1:p.Val823Leu
NP_001393747.1:p.Val1246Leu
NP_001393748.1:p.Val1246Leu
NP_001393749.1:p.Val1246Leu
NP_001393750.1:p.Val1246Leu
NP_001393752.1:p.Val1043Leu
NP_001393753.1:p.Val1246Leu
NP_001393754.1:p.Val1246Leu
NP_001393755.1:p.Val1289Leu
NP_001393756.1:p.Val1246Leu
NP_001393757.1:p.Val1246Leu
NP_001393758.1:p.Val1043Leu
NP_001393759.1:p.Val1246Leu
NP_001393760.1:p.Val272Leu
NP_001393761.1:p.Val294Leu
NP_001394291.1:p.Val660Leu
LRG_219t1:c.4033G>T
LRG_219:g.28664G>T
LRG_219p1:p.Val1345Leu
NC_000002.11:g.48033949G>T
NM_000179.2:c.4033G>T
NR_176256.1:n.2963G>T
NR_176257.1:n.4294G>T
NR_176258.1:n.4223G>T
NR_176259.1:n.4122G>T
NR_176260.1:n.2067G>T
NR_176261.1:n.4004G>T

Protein change:

V1043L

Molecular consequence:

NM_000179.3:c.4033G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001281492.2:c.3643G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001281493.2:c.3127G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001281494.2:c.3127G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406795.1:c.4129G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406796.1:c.4033G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406797.1:c.3736G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406798.1:c.3859G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406799.1:c.3508G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406803.1:c.3169G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406804.1:c.3955G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406805.1:c.3736G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406806.1:c.3508G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406807.1:c.3508G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406809.1:c.4033G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406811.1:c.3127G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406812.1:c.3127G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406813.1:c.4039G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406814.1:c.3127G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406815.1:c.3127G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406816.1:c.3127G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406817.1:c.2467G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406818.1:c.3736G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406819.1:c.3736G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406820.1:c.3736G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406821.1:c.3736G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406823.1:c.3127G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406824.1:c.3736G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406825.1:c.3736G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406826.1:c.3865G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406827.1:c.3736G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406828.1:c.3736G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406829.1:c.3127G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406830.1:c.3736G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406831.1:c.814G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406832.1:c.880G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407362.1:c.1978G>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

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matrix metalloproteinase-14 preproprotein [Homo sapiens]
matrix metalloproteinase-14 preproprotein [Homo sapiens]
gi|4826834|ref|NP_004986.1|

Protein
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002626238	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Nov 30, 2015)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002626238

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Nov 30, 2015)

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, SCV002626238.2

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

Description

The p.V1345L variant (also known as c.4033G>T), located in coding exon 10 of the MSH6 gene, results from a G to T substitution at nucleotide position 4033. The valine at codon 1345 is replaced by leucine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 115000 alleles tested) in our clinical cohort. This amino acid position is not well conserved however, leucine is a reference amino acid in several species. This alteration is predicted to be benign and tolerated by PolyPhen and SIFT in silico analyses, respectively. In addition, the CoDP in silico tool predicts this alteration to have minor impact on molecular function, with a score of 0.004 (Terui H et al. J. Biomed. Sci. 2013;20:25). Since supporting evidence is limited at this time, the clinical significance of p.V1345L 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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