Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001377905 | SCV001575355 | likely pathogenic | Nephronophthisis | 2020-08-09 | criteria provided, single submitter | clinical testing | This sequence change results in a frameshift in the INVS gene (p.Gln1035Argfs*71). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 31 amino acids of the INVS protein and extend the protein by an additional 39 amino acids. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of nephronophthisis (Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant results in an extension of the INVS protein. Other variant(s) that result in a similarly extended protein product (p.Asn1042Thrfs*64) have been observed in individuals with INVS-related conditions (PMID: 23559409). This suggests that these extensions may be clinically significant. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |