ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.2292G>A (p.Ala764=)

gnomAD frequency: 0.00001  dbSNP: rs772565983
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000728641 SCV000856241 uncertain significance not provided 2017-08-08 criteria provided, single submitter clinical testing
Mendelics RCV000990078 SCV001140861 pathogenic Niemann-Pick disease, type C1 2019-05-28 criteria provided, single submitter clinical testing
Invitae RCV000990078 SCV001573918 pathogenic Niemann-Pick disease, type C1 2023-11-09 criteria provided, single submitter clinical testing This sequence change affects codon 764 of the NPC1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the NPC1 protein. RNA analysis indicates that this variant induces altered splicing and likely results in the loss of Ala750_Gly765 amino acid residue(s), but is expected to preserve the integrity of the reading-frame. This variant is present in population databases (rs772565983, gnomAD 0.008%). This variant has been observed in individual(s) with Niemann-Pick type C (PMID: 11479732, 20718790, 32138288). This variant is also known as IVS16-82G>A, p.A750del16 or p.A750-G765del . ClinVar contains an entry for this variant (Variation ID: 593560). Studies have shown that this variant results in the activation of a cryptic splice site in Exon 15 (PMID: 11479732, 20718790). This variant disrupts the p.Ala764Val amino acid residue in NPC1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 24676439, 26790753, 26910362). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Natera, Inc. RCV000990078 SCV002095192 likely pathogenic Niemann-Pick disease, type C1 2020-07-28 no assertion criteria provided clinical testing

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