Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Human Genetics, |
RCV000659820 | SCV000781679 | pathogenic | Kabuki syndrome 1 | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002530556 | SCV003440523 | pathogenic | Kabuki syndrome | 2022-04-07 | criteria provided, single submitter | clinical testing | This premature translational stop signal has been observed in individual(s) with Kabuki syndrome (PMID: 21280141). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 547499). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg4960*) in the KMT2D gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KMT2D are known to be pathogenic (PMID: 22126750). |
Prevention |
RCV004533449 | SCV004754683 | pathogenic | KMT2D-related disorder | 2024-01-19 | criteria provided, single submitter | clinical testing | The KMT2D c.14878C>T variant is predicted to result in premature protein termination (p.Arg4960*). This variant has been reported as a recurring de novo variant in multiple individuals with Kabuki Syndrome (Paulussen et al. 2011. PubMed ID: 21280141; So et al. 2021. PubMed ID: 33314698; internal cases at PreventionGenetics). This variant has not been reported in a large population database, indicating this variant is rare. Nonsense variants in KMT2D are expected to be pathogenic. Given the evidence, we interpret this variant as pathogenic. |