ClinVar Miner

Submissions for variant NM_194454.3(KRIT1):c.1730+4_1730+7del

dbSNP: rs1563244596
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics, part of Exact Sciences RCV000721856 SCV000853003 pathogenic not provided 2015-08-13 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001066958 SCV001231983 pathogenic Cerebral cavernous malformation 2023-03-29 criteria provided, single submitter clinical testing This variant is also known as IVS15del(+4->+7). ClinVar contains an entry for this variant (Variation ID: 590717). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 12404106). For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with cerebral cavernous malformations (PMID: 12404106; Invitae). This sequence change falls in intron 16 of the KRIT1 gene. It does not directly change the encoded amino acid sequence of the KRIT1 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency).
Mayo Clinic Laboratories, Mayo Clinic RCV000721856 SCV005413787 pathogenic not provided 2024-01-26 criteria provided, single submitter clinical testing PM2, PS4_moderate, PVS1
GeneDx RCV000721856 SCV005881985 likely pathogenic not provided 2024-09-09 criteria provided, single submitter clinical testing RNA studies demonstrate a damaging effect resulting in the presence of an aberrant transcript missing exon 15, which leads to a premature stop codon and nonsense mediated decay (PMID: 12404106); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on splicing; This variant is associated with the following publications: (PMID: 12404106, 23595507)

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