Submissions for variant NM_194454.3(KRIT1):c.1201_1204del (p.Gln401fs)

dbSNP: rs1057517753

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000414484	SCV000490587	pathogenic	not provided	2023-07-18	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 23595507, 27649701, 22699465, 18300272, 20884211, 18383594, 33651268)
PreventionGenetics, part of Exact Sciences	RCV000414484	SCV000852966	pathogenic	not provided	2016-06-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000816950	SCV000957480	pathogenic	Cerebral cavernous malformation	2023-07-12	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln401Thrfs*10) in the KRIT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KRIT1 are known to be pathogenic (PMID: 10508515, 11222804, 12404106, 24689081). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with cerebral cavernous malformations (PMID: 2359550, 18300272, 20884211, 22699465, 27649701; Invitae). This variant is also known as c.1197_1200delCAAA. ClinVar contains an entry for this variant (Variation ID: 372398). For these reasons, this variant has been classified as Pathogenic.
Genetics and Molecular Pathology, SA Pathology	RCV003447526	SCV004175585	pathogenic	Hereditary cavernous hemangioma of brain	2022-06-20	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000414484	SCV005413788	pathogenic	not provided	2024-06-05	criteria provided, single submitter	clinical testing	PP1_strong, PP4, PM2, PS4_moderate, PVS1
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000816950	SCV001366349	uncertain significance	Cerebral cavernous malformation	2016-01-01	flagged submission	clinical testing	This variant was classified as: Uncertain significance. The following ACMG criteria were applied in classifying this variant: PM2,PP4,PP5.
Laboratory of Medical Genetics, University of Torino	RCV000816950	SCV001976510	pathogenic	Cerebral cavernous malformation	2021-10-06	no assertion criteria provided	research