Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001309697 | SCV001499204 | uncertain significance | not provided | 2022-09-07 | criteria provided, single submitter | clinical testing | This variant, c.2957_2990delins34, is a complex sequence change that results in the deletion of 12 and insertion of 12 different amino acid(s) in the MSH3 protein (p.Gly986_Phe997delins12). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 1011839). This variant has not been reported in the literature in individuals affected with MSH3-related conditions. Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. |
| Ambry Genetics | RCV003294252 | SCV004008602 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2024-10-17 | criteria provided, single submitter | clinical testing | The c.2957_2990DEL34INS34 variant, located in coding exon 21 of the MSH3 gene, results from an in-frame deletion of 34 nucleotides and insertion of 34 different nucleotides at nucleotide positions 2957 to 2990, resulting in amino acid substitutions at codons 986 to 997 (p.G986_F997delinsVSAHQILTSDTY). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid region is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may weaken the native splice donor site and may result in the creation or strengthening of a novel splice donor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |