Submissions for variant NM_000251.3(MSH2):c.547C>T (p.Gln183Ter)

dbSNP: rs63750037

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)	RCV000076634	SCV000107669	pathogenic	Lynch syndrome	2013-09-05	reviewed by expert panel	research	Coding sequence variation resulting in a stop codon
Ambry Genetics	RCV000561236	SCV000676090	pathogenic	Hereditary cancer-predisposing syndrome	2022-11-04	criteria provided, single submitter	clinical testing	The p.Q183* pathogenic mutation (also known as c.547C>T), located in coding exon 3 of the MSH2 gene, results from a C to T substitution at nucleotide position 547. This changes the amino acid from a glutamine to a stop codon within coding exon 3. This mutation was originally reported in a Portuguese patient who met clinical criteria for Lynch syndrome (Fidalgo P et al. Europ J Hum Genet. 2000 Jan;8(1):49-53). This mutation was also identified in an Australian female diagnosed with early-onset colorectal cancer at 28 years. Her colorectal tumor displayed microsatellite instability and showed absence of MSH2 staining on immunohistochemistry (Ward R et al. J. Cancer Res. Clin. Oncol. 2002 Aug;128(8):403-11). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Color Diagnostics, LLC DBA Color Health	RCV000561236	SCV000905221	pathogenic	Hereditary cancer-predisposing syndrome	2020-01-15	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 3 of the MSH2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MSH2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Revvity Omics, Revvity	RCV001781399	SCV002017558	pathogenic	not provided	2019-03-01	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003452950	SCV004187994	pathogenic	Lynch syndrome 1	2023-07-27	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.