Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000485302 | SCV000569459 | uncertain significance | not provided | 2016-02-25 | criteria provided, single submitter | clinical testing | This duplication of 56 nucleotides in MSH6 is denoted c.4022_4077dup56 at the cDNA level and p.Leu1360LysfsX5 (p.L1360KfsX5) at the protein level. The normal sequence is AGTG[dup56]TTAT. The duplication causes a frameshift, which changes a Leucine to a Lysine at codon 1360, the last residue of the MSH6 gene, and results in an extension of the protein by five amino acids. This variant occurs in the C-terminal region of MSH6, which is a binding site for MSH2 (Kariola 2002). MSH6 c.4022_4077dup56 has not, to our knowledge, been reported in the literature. Based on currently available information, it is unclear whether MSH6 c.4022_4077dup56 is pathogenic or benign. We consider it to be a variant of uncertain significance. |
Ambry Genetics | RCV000572669 | SCV000662484 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-27 | criteria provided, single submitter | clinical testing | The c.4022_4077dup56 variant, located in coding exon 10 of the MSH6 gene, results from a duplication of 56 nucleotides at nucleotide position 4022 to 4077, causing a translational frameshift with a predicted alternate stop codon (p.L1360Kfs*5). This alteration occurs at the 3' terminus of MSH6 gene, is not expected to trigger nonsense-mediated mRNAdecay, and results in the elongation of the protein by 3 amino acids. This frameshift impacts only the last amino acid of the native protein. The exact functional effect of the altered amino acids is unknown. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV000703204 | SCV000832092 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2024-01-23 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu1360Lysfs*5) in the MSH6 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1 amino acid(s) of the MSH6 protein. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. ClinVar contains an entry for this variant (Variation ID: 420575). 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. |
Mendelics | RCV000708899 | SCV000837936 | uncertain significance | Lynch syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing |