ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.3734_3735del (p.Pro1245fs) (rs1064794009)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000480939 SCV000567580 pathogenic not provided 2015-08-13 criteria provided, single submitter clinical testing The c.3734_3735delCT deletion in the NPC1 gene has been reported previously in association with Niemann-Pick disease, type C (Tarugi et al., 2002; Zhang et al., 2014; Yang et al., 2015). The deletion causes a frameshift starting with codon Proline 1245, changes this amino acid to an Arginine residue and creates a premature Stop codon at position 12 of the new reading frame, denoted p.Pro1245ArgfsX12. This variant is predicted to cause loss of normal protein function through protein truncation. Therefore, we interpret c.3734_3735delCT in NPC1 as a pathogenic variant.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000480939 SCV000706895 likely pathogenic not provided 2017-03-20 criteria provided, single submitter clinical testing
Invitae RCV000984201 SCV001589683 pathogenic Niemann-Pick disease type C1 2020-10-25 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the NPC1 gene (p.Pro1245Argfs*12). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 34 amino acids of the NPC1 protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with Niemann-Pick Type C (PMID: 12401890, 23597521, 24915861). ClinVar contains an entry for this variant (Variation ID: 419641). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000984201 SCV001132260 likely pathogenic Niemann-Pick disease type C1 2015-04-27 no assertion criteria provided clinical testing

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