Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000166702 | SCV000217511 | uncertain significance | Hereditary cancer-predisposing syndrome | 2014-11-17 | criteria provided, single submitter | clinical testing | The c.813_815delGGA variant (also known as p.E272del) located in coding exon 4 of the MSH6 gene. This variant results from an in-frame deletion of 3 nucleotides at positions 813 to 815, causing the removal of a well-conserved glutamate residue at codon 272. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.004% (greater than 24000 alleles tested) in our clinical cohort. Since supporting evidence is limited at this time, the clinical significance of c.813_815delGGA remains unclear. |
| Color Diagnostics, |
RCV000166702 | SCV001735066 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-20 | criteria provided, single submitter | clinical testing | This variant causes an in-frame deletion of one amino acid at exon 4 of the MSH6 protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MSH6-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Invitae | RCV002516506 | SCV003322377 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-02-01 | criteria provided, single submitter | clinical testing | 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. 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: 187020). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.813_815del, results in the deletion of 1 amino acid(s) of the MSH6 protein (p.Glu272del), but otherwise preserves the integrity of the reading frame. |
| All of Us Research Program, |
RCV003995525 | SCV004837052 | uncertain significance | Lynch syndrome | 2023-05-04 | criteria provided, single submitter | clinical testing | This variant causes an in-frame deletion of one amino acid at exon 4 of the MSH6 protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MSH6-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |