ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.350_351AG[1] (p.Gln119fs) (rs759075595)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000410714 SCV000485383 pathogenic Niemann-Pick disease type C1 2016-09-09 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000781671 SCV000919894 pathogenic Niemann-Pick disease, type C 2017-12-04 criteria provided, single submitter clinical testing Variant summary: The NPC1 c.352_353delAG (p.Gln119ValfsX8) variant 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. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.1819C>T, p.Arg607X; c.3742_3745delCTCA, p.Leu1248fsX3). One in silico tool predicts a damaging outcome for this variant. This variant was found in 2/246198 control chromosomes at a frequency of 0.0000081, which does not exceed the estimated maximal expected allele frequency of a pathogenic NPC1 variant (0.0027735). The variant has been reported in affected individuals in the literature, and one functional study showed the variant results in reduced mRNA due to non-sense mediated decay (Marcias-Vidal_2009). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Natera, Inc. RCV000410714 SCV001459999 pathogenic Niemann-Pick disease type C1 2020-09-16 no assertion criteria provided clinical testing

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