Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000074688 | SCV000107891 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
Gene |
RCV000482414 | SCV000566298 | pathogenic | not provided | 2015-04-17 | criteria provided, single submitter | clinical testing | This duplication of one nucleotide in MSH6 is denoted c.1819dupA at the cDNA level and p.Thr607AsnfsX33 (T607NfsX33) at the protein level. The normal sequence, with the base that is duplicated in brackets, is TAAA[A]CAAT. The duplication causes a frameshift, which changes a Threonine to an Asparagine at codon 607, and creates a premature stop codon at position 33 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. we consider this variant to be pathogenic. |
Ambry Genetics | RCV002408571 | SCV002710407 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-11-16 | criteria provided, single submitter | clinical testing | The c.1819dupA pathogenic mutation, located in coding exon 4 of the MSH6 gene, results from a duplication of A at nucleotide position 1819, causing a translational frameshift with a predicted alternate stop codon (p.T607Nfs*33). This variant was identified in a cohort of 4439 women with ovarian cancer undergoing multigene panel testing at one laboratory (Carter NJ et al. Gynecol Oncol, 2018 12;151:481-488). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. |
Myriad Genetics, |
RCV003450932 | SCV004185815 | pathogenic | Lynch syndrome 5 | 2023-08-15 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |