Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002454787 | SCV002615464 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-05-07 | criteria provided, single submitter | clinical testing | The c.3365_3366insTT pathogenic mutation, located in coding exon 5 of the MSH6 gene, results from an insertion of two nucleotides at position 3365, causing a translational frameshift with a predicted alternate stop codon (p.Q1122Hfs*24). 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, |
RCV003454112 | SCV004187289 | pathogenic | Lynch syndrome 5 | 2023-08-22 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
Baylor Genetics | RCV003464451 | SCV004198128 | likely pathogenic | Endometrial carcinoma | 2022-10-05 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV004005624 | SCV004842702 | likely pathogenic | Lynch syndrome | 2024-01-22 | criteria provided, single submitter | clinical testing | The c.3365_3366insTT (p.Gln1122Hisfs*24) variant in the MSH6 gene, that encodes for mutS homolog 6, introduces a premature translation termination codon in exon 5, resulting in an absent or disrupted protein product. Loss-of-function variants in MSH6 are well known to be pathogenic and ClinGen score shows sufficient evidence of haploinsufficiency of this gene (PMID: 9354786, 11709755, 20028993, 25318681). Truncating variants downstream of this variant are reported to be pathogenic in the literature (PMID: 18301448, 28514183, 28528517) and by several ClinVar submitters (ClinVar ID: 89377, 141166). This variant is found to be absent in the general population database, gnomAD and interpreted as pathogenic by a ClinVar submitter (ClinVar ID: 1730649). Therefore, the c.3365_3366insTT (p.Gln1122Hisfs*24) variant in the MSH6 gene is classified as likely pathogenic. |