ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.3293C>T (p.Thr1098Ile) (rs746285672)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Broad Institute Rare Disease Group,Broad Institute RCV001004881 SCV001164365 uncertain significance Niemann-Pick disease type C1 2018-12-03 criteria provided, single submitter research The heterozygous p.Thr1098Ile variant in NPC1 was identified by our study in the compound heterozygous state, with a VUS, in one individual with Niemann-Pick disease. The p.Thr1098Ile variant in NPC1 has not been previously reported in individuals with Niemann-Pick disease but has been identified in 0.003249% (1/30780) of South Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs746285672). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Thr1098Ile variant is uncertain. ACMG/AMP Criteria applied: PM2, PP3 (Richards 2015).

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