ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.688_693del (p.Ser230_Val231del) (rs758687942)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000492895 SCV000344636 uncertain significance not provided 2016-08-09 criteria provided, single submitter clinical testing
GeneDx RCV000492895 SCV000581824 pathogenic not provided 2017-04-28 criteria provided, single submitter clinical testing The c.688_693delTCTGTG variant has been reported previously in association with Niemann-Pickdisease, type C (NPC) in patients who also harbored a second variant in the NPC1 gene (Sun et al.,2001; Imrie et al., 2015). The c.688_693delTCTGTG variant causes the loss of a Serine codon atposition 230 and the loss of a Valine codon at position 231, denoted p.Ser230_Val231. Thec.688_693delTCTGTG variant is not observed at a significant frequency in large population cohorts(Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). In silico analysispredicts this variant is probably damaging to the protein structure/function. In summary, we interpretc.688_693delTCTGTG as pathogenic.
Counsyl RCV000669390 SCV000794138 uncertain significance Niemann-Pick disease type C1 2017-09-15 criteria provided, single submitter clinical testing
Invitae RCV000669390 SCV001410264 likely pathogenic Niemann-Pick disease type C1 2019-10-31 criteria provided, single submitter clinical testing This variant, c.688_693del, results in the deletion of 2 amino acid(s) of the NPC1 protein (p.Ser230_Val231del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs758687942, ExAC 0.01%). This variant has been observed in individuals affected with NPC1-related conditions (PMID: 11349231, 19744920, 26666848). ClinVar contains an entry for this variant (Variation ID: 290134). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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