Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001305492 | SCV001494829 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2022-09-23 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser900*) in the MSH2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 35 amino acid(s) of the MSH2 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with hereditary breast and ovarian cancer (HBOC) (PMID: 24549055). ClinVar contains an entry for this variant (Variation ID: 237392). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Fulgent Genetics, |
RCV005025381 | SCV005661134 | likely pathogenic | Lynch syndrome 1; Muir-Torré syndrome; Mismatch repair cancer syndrome 2 | 2024-06-13 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV005365179 | SCV006031376 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-12-17 | criteria provided, single submitter | clinical testing | The p.S900* variant (also known as c.2699C>G), located in coding exon 16 of the MSH2 gene, results from a C to G substitution at nucleotide position 2699. This changes the amino acid from a serine to a stop codon within coding exon 16. This alteration occurs at the 3' terminus of theMSH2 gene, is not expected to trigger nonsense-mediated mRNAdecay, and impacts the last 3.75% of the protein. The exact functional effect of this alteration is unknown. This variant was reported in individual(s) with features consistent with MSH2-related Lynch syndrome (Castéra L et al. Eur J Hum Genet, 2014 Nov;22:1305-13). Based on the available evidence, the clinical significance of this variant remains unclear. |