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NM_000179.3(MSH6):c.3762A>C (p.Glu1254Asp) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Apr 22, 2018
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:
RCV002349379.2

Allele description [Variation Report for NM_000179.3(MSH6):c.3762A>C (p.Glu1254Asp)]

NM_000179.3(MSH6):c.3762A>C (p.Glu1254Asp)

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.3762A>C (p.Glu1254Asp)
HGVS:
  • NC_000002.12:g.47806319A>C
  • NG_007111.1:g.28173A>C
  • NG_008397.1:g.104357T>G
  • NM_000179.3:c.3762A>CMANE SELECT
  • NM_001281492.2:c.3372A>C
  • NM_001281493.2:c.2856A>C
  • NM_001281494.2:c.2856A>C
  • NM_001406795.1:c.3858A>C
  • NM_001406796.1:c.3762A>C
  • NM_001406797.1:c.3465A>C
  • NM_001406798.1:c.3588A>C
  • NM_001406799.1:c.3237A>C
  • NM_001406800.1:c.3762A>C
  • NM_001406801.1:c.3465A>C
  • NM_001406802.1:c.3858A>C
  • NM_001406803.1:c.2898A>C
  • NM_001406804.1:c.3684A>C
  • NM_001406805.1:c.3465A>C
  • NM_001406806.1:c.3237A>C
  • NM_001406807.1:c.3237A>C
  • NM_001406808.1:c.3762A>C
  • NM_001406809.1:c.3762A>C
  • NM_001406811.1:c.2856A>C
  • NM_001406812.1:c.2856A>C
  • NM_001406813.1:c.3768A>C
  • NM_001406814.1:c.2856A>C
  • NM_001406815.1:c.2856A>C
  • NM_001406816.1:c.2856A>C
  • NM_001406817.1:c.2196A>C
  • NM_001406818.1:c.3465A>C
  • NM_001406819.1:c.3465A>C
  • NM_001406820.1:c.3465A>C
  • NM_001406821.1:c.3465A>C
  • NM_001406822.1:c.3465A>C
  • NM_001406823.1:c.2856A>C
  • NM_001406824.1:c.3465A>C
  • NM_001406825.1:c.3465A>C
  • NM_001406826.1:c.3594A>C
  • NM_001406827.1:c.3465A>C
  • NM_001406828.1:c.3465A>C
  • NM_001406829.1:c.2856A>C
  • NM_001406830.1:c.3465A>C
  • NM_001406831.1:c.543A>C
  • NM_001406832.1:c.609A>C
  • NM_001407362.1:c.1707A>C
  • NP_000170.1:p.Glu1254Asp
  • NP_000170.1:p.Glu1254Asp
  • NP_001268421.1:p.Glu1124Asp
  • NP_001268422.1:p.Glu952Asp
  • NP_001268423.1:p.Glu952Asp
  • NP_001393724.1:p.Glu1286Asp
  • NP_001393725.1:p.Glu1254Asp
  • NP_001393726.1:p.Glu1155Asp
  • NP_001393727.1:p.Glu1196Asp
  • NP_001393728.1:p.Glu1079Asp
  • NP_001393729.1:p.Glu1254Asp
  • NP_001393730.1:p.Glu1155Asp
  • NP_001393731.1:p.Glu1286Asp
  • NP_001393732.1:p.Glu966Asp
  • NP_001393733.1:p.Glu1228Asp
  • NP_001393734.1:p.Glu1155Asp
  • NP_001393735.1:p.Glu1079Asp
  • NP_001393736.1:p.Glu1079Asp
  • NP_001393737.1:p.Glu1254Asp
  • NP_001393738.1:p.Glu1254Asp
  • NP_001393740.1:p.Glu952Asp
  • NP_001393741.1:p.Glu952Asp
  • NP_001393742.1:p.Glu1256Asp
  • NP_001393743.1:p.Glu952Asp
  • NP_001393744.1:p.Glu952Asp
  • NP_001393745.1:p.Glu952Asp
  • NP_001393746.1:p.Glu732Asp
  • NP_001393747.1:p.Glu1155Asp
  • NP_001393748.1:p.Glu1155Asp
  • NP_001393749.1:p.Glu1155Asp
  • NP_001393750.1:p.Glu1155Asp
  • NP_001393751.1:p.Glu1155Asp
  • NP_001393752.1:p.Glu952Asp
  • NP_001393753.1:p.Glu1155Asp
  • NP_001393754.1:p.Glu1155Asp
  • NP_001393755.1:p.Glu1198Asp
  • NP_001393756.1:p.Glu1155Asp
  • NP_001393757.1:p.Glu1155Asp
  • NP_001393758.1:p.Glu952Asp
  • NP_001393759.1:p.Glu1155Asp
  • NP_001393760.1:p.Glu181Asp
  • NP_001393761.1:p.Glu203Asp
  • NP_001394291.1:p.Glu569Asp
  • LRG_219t1:c.3762A>C
  • LRG_219:g.28173A>C
  • LRG_219p1:p.Glu1254Asp
  • NC_000002.11:g.48033458A>C
  • NM_000179.2:c.3762A>C
  • NR_176256.1:n.2692A>C
  • NR_176257.1:n.4023A>C
  • NR_176258.1:n.3952A>C
  • NR_176259.1:n.3851A>C
  • NR_176260.1:n.1796A>C
  • NR_176261.1:n.3733A>C
Protein change:
E1079D
Molecular consequence:
  • NM_000179.3:c.3762A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281492.2:c.3372A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281493.2:c.2856A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281494.2:c.2856A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406795.1:c.3858A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406796.1:c.3762A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406797.1:c.3465A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406798.1:c.3588A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406799.1:c.3237A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406800.1:c.3762A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406801.1:c.3465A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406802.1:c.3858A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406803.1:c.2898A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406804.1:c.3684A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406805.1:c.3465A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406806.1:c.3237A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406807.1:c.3237A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406808.1:c.3762A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406809.1:c.3762A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406811.1:c.2856A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406812.1:c.2856A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406813.1:c.3768A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406814.1:c.2856A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406815.1:c.2856A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406816.1:c.2856A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406817.1:c.2196A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406818.1:c.3465A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406819.1:c.3465A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406820.1:c.3465A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406821.1:c.3465A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406822.1:c.3465A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406823.1:c.2856A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406824.1:c.3465A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406825.1:c.3465A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406826.1:c.3594A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406827.1:c.3465A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406828.1:c.3465A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406829.1:c.2856A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406830.1:c.3465A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406831.1:c.543A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406832.1:c.609A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407362.1:c.1707A>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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002620351Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Apr 22, 2018) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Classification of mismatch repair gene missense variants with PON-MMR.

Ali H, Olatubosun A, Vihinen M.

Hum Mutat. 2012 Apr;33(4):642-50. doi: 10.1002/humu.22038.

PubMed [citation]
PMID:
22290698

Details of each submission

From Ambry Genetics, SCV002620351.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

The p.E1254D variant (also known as c.3762A>C), located in coding exon 8 of the MSH6 gene, results from an A to C substitution at nucleotide position 3762. The glutamic acid at codon 1254 is replaced by aspartic acid, an amino acid with highly similar properties. This alteration was reported as a somatic alteration in the lung cancer of a 78-year-old patient (Lin L et al. Int. J. Clin. Exp. Pathol. 2017;10(9):9583-9590). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. In addition, the CoDP in silico tool predicts this alteration to have a minor impact on molecular function, with a score of 0.027, and this alteration is predicted neutral by the PON-MMR in silico tool (Terui H et al. J. Biomed. Sci. 2013 Apr;20:25; Ali H et. al. Hum. Mutat. 2012 Apr;33:642-50). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 1, 2024