ClinVar Miner

Submissions for variant NM_003482.4(KMT2D):c.14878C>T (p.Arg4960Ter)

dbSNP: rs1555185969
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Human Genetics, Inc, Center for Human Genetics, Inc 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).
PreventionGenetics, part of Exact Sciences 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.

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