ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.3742_3745del (p.Leu1248fs) (rs774943545)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000576310 SCV000678022 likely pathogenic Niemann-Pick disease type C1 2014-01-02 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000589877 SCV000696421 pathogenic Niemann-Pick disease, type C 2017-07-03 criteria provided, single submitter clinical testing Variant summary: The NPC1 c.3742_3745delCTCA (p.Leu1248Valfs) variant (also known as 3741_3744delACTC) results in a premature termination codon, predicted to cause a truncated or absent NPC1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. This variant was found in 5/121194 control chromosomes from ExAC at a frequency of 0.0000413, which does not exceed the estimated maximal expected allele frequency of a pathogenic NPC1 variant (0.0027735). The variant was detected in at least three patients with NPC. Variant downsteam of this variant c.3744_3747 delCAGT has also been reported in affected individual and listed as "DM-disease mutation" in HGMD, suggesitng this location is a mutation hotspot. Taken together, this variant is classified as pathogenic.

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