NM_000179.3(MSH6):c.3850dup (p.Thr1284fs) AND Lynch syndrome

Clinical significance:Likely pathogenic (Last evaluated: Dec 1, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_000179.3(MSH6):c.3850dup (p.Thr1284fs)]

NM_000179.3(MSH6):c.3850dup (p.Thr1284fs)

MSH6:mutS homolog 6 [Gene - OMIM - HGNC]
Variant type:
Cytogenetic location:
Genomic location:
Preferred name:
NM_000179.3(MSH6):c.3850dup (p.Thr1284fs)
  • NC_000002.12:g.47806500dup
  • NG_007111.1:g.28354dup
  • NG_008397.1:g.104176dup
  • NM_000179.2:c.3850dup
  • NM_000179.3:c.3850dupMANE SELECT
  • NM_001281492.2:c.3460dup
  • NM_001281493.2:c.2944dup
  • NM_001281494.2:c.2944dup
  • NP_000170.1:p.Thr1284fs
  • NP_000170.1:p.Thr1284fs
  • NP_001268421.1:p.Thr1154fs
  • NP_001268422.1:p.Thr982fs
  • NP_001268423.1:p.Thr982fs
  • LRG_219t1:c.3850dup
  • LRG_219:g.28354dup
  • LRG_219p1:p.Thr1284fs
  • NC_000002.11:g.48033638_48033639insA
  • NC_000002.11:g.48033639dup
  • NM_000179.2:c.3850dupA
Protein change:
dbSNP: rs1553333421
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000179.3:c.3850dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001281492.2:c.3460dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001281493.2:c.2944dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001281494.2:c.2944dup - frameshift variant - [Sequence Ontology: SO:0001589]


Lynch syndrome
Familial nonpolyposis colon cancer
MONDO: MONDO:0005835; MedGen: C4552100; OMIM: PS120435

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000917748Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely pathogenic
(Dec 1, 2017)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000917748.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided


Variant summary: The MSH6 c.3850dupA (p.Thr1284AsnfsX5) variant results in a premature termination codon, predicted to cause a truncated or absent MSH6 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool predicts a damaging outcome for this variant. A variant that affects the same codon and leads to an equivalent change at the protein level (c.3847_3850dupATTA (p.Thr1284Asnfs)) as the variant of interest has been classified as pathogenic by multiple laboratories. Also, truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.3938_3941dupTTCA (p.Gln1314fsX6), c.3939_3957dupTCAAAAGGGACATAGAAAA (p.Ala1320fsX5), c.3939_3940dupTC (p.Gln1314fsX14)). This variant is absent in 276776 control chromosomes. In addition, one diagnostic laboratory classified this variant as pathogenic. The variant of interest has not, to our knowledge, been reported in affected individuals via publications; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely pathogenic.

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

Last Updated: Oct 25, 2021

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