Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002434052 | SCV002748497 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-12-20 | criteria provided, single submitter | clinical testing | The p.E948* pathogenic mutation (also known as c.2842G>T), located in coding exon 4 of the MSH6 gene, results from a G to T substitution at nucleotide position 2842. This changes the amino acid from a glutamic acid to a stop codon within coding exon 4. 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. |
MVZ Praenatalmedizin und Genetik Nuernberg | RCV000856619 | SCV000999083 | pathogenic | Lynch syndrome 5 | 2019-02-28 | no assertion criteria provided | clinical testing | GnomAD shows no entry for this variant (very rare or private variant). This variant in exon 4 of MSH6 results in a premature stop-codon. Thus, we expect a loss of function. Accordingly, ClinVar lists several nonsense mutations further downstream (e.g. p.Tyr977Ter) with pathogenic classification (expert panel). We therefore classify this variant as pathogenic. |