ClinVar Miner

Submissions for variant NM_194454.3(KRIT1):c.1201_1204del (p.Gln401fs) (rs1057517753)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000414484 SCV000490587 pathogenic not provided 2016-11-21 criteria provided, single submitter clinical testing The c.1201_1204delCAAA pathogenic variant in the KRIT1 gene has been previously reported in patients with CCM (Rajakulendran et al., 2011; Zhao et al., 2011). The c.1201_1204delCAAA variant causes a frameshift starting with codon Glutamine 401, changes this amino acid to a Threonine residue and creates a premature Stop codon at position 10 of the new reading frame, denoted p.Gln401ThrfsX10. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Therefore, c.1201_1204delCAAA is considered a pathogenic variant.
PreventionGenetics,PreventionGenetics RCV000414484 SCV000852966 pathogenic not provided 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000816950 SCV000957480 pathogenic Cerebral cavernous malformation 2019-09-28 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. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with cerebral cavernous malformations (PMID: 27649701,22699465, 20884211, 2359550, 18300272, Invitae). ClinVar contains an entry for this variant (Variation ID: 372398). This variant is also known as c.1197_1200delCAAA in the literature. Loss-of-function variants in KRIT1 are known to be pathogenic (PMID: 10508515, 11222804, 12404106). For these reasons, this variant has been classified as Pathogenic.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000816950 SCV001366349 uncertain significance Cerebral cavernous malformation 2016-01-01 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The following ACMG criteria were applied in classifying this variant: PM2,PP4,PP5.

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