NM_000251.3(MSH2):c.336C>A (p.Ser112=) AND Lynch syndrome I

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Jan 12, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:

Allele description [Variation Report for NM_000251.3(MSH2):c.336C>A (p.Ser112=)]

NM_000251.3(MSH2):c.336C>A (p.Ser112=)

MSH2:mutS homolog 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000251.3(MSH2):c.336C>A (p.Ser112=)
  • NC_000002.12:g.47408525C>A
  • NG_007110.2:g.10402C>A
  • NM_000251.2:c.336C>A
  • NM_000251.3:c.336C>AMANE SELECT
  • NM_001258281.1:c.138C>A
  • NP_000242.1:p.Ser112=
  • NP_000242.1:p.Ser112=
  • NP_001245210.1:p.Ser46=
  • LRG_218t1:c.336C>A
  • LRG_218:g.10402C>A
  • LRG_218p1:p.Ser112=
  • NC_000002.11:g.47635664C>A
  • NM_000251.1:c.336C>A
  • p.S112S
  • p.Ser112Ser
dbSNP: rs34312619
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000251.2:c.336C>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_000251.3:c.336C>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001258281.1:c.138C>A - synonymous variant - [Sequence Ontology: SO:0001819]


Lynch syndrome I (COCA1)
COLON CANCER, FAMILIAL NONPOLYPOSIS, TYPE 1; MSH2-Related Hereditary Non-Polyposis Colon Cancer; Lynch syndrome 1; See all synonyms [MedGen]
MONDO: MONDO:0007356; MedGen: C2936783; Orphanet: 144; OMIM: 120435

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000430912Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Uncertain significance
(Jan 12, 2018)
germlineclinical testing

Citation Link,

SCV000784762Counsylcriteria provided, single submitter
Likely benign
(Nov 13, 2017)
unknownclinical testing

PubMed (2)
[See all records that cite these PMIDs]


Citation Link

Summary from all submissions

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



Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer).

Hampel H, Frankel WL, Martin E, Arnold M, Khanduja K, Kuebler P, Nakagawa H, Sotamaa K, Prior TW, Westman J, Panescu J, Fix D, Lockman J, Comeras I, de la Chapelle A.

N Engl J Med. 2005 May 5;352(18):1851-60.

PubMed [citation]

RBP-Var: a database of functional variants involved in regulation mediated by RNA-binding proteins.

Mao F, Xiao L, Li X, Liang J, Teng H, Cai W, Sun ZS.

Nucleic Acids Res. 2016 Jan 4;44(D1):D154-63. doi: 10.1093/nar/gkv1308. Epub 2015 Dec 3.

PubMed [citation]

Details of each submission

From Illumina Clinical Services Laboratory,Illumina, SCV000430912.3

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


This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

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

From Counsyl, SCV000784762.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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