ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.3591+1G>A (rs786200877)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000003107 SCV000220771 likely pathogenic Niemann-Pick disease type C1 2014-10-07 criteria provided, single submitter literature only
Integrated Genetics/Laboratory Corporation of America RCV001193398 SCV001362186 pathogenic Niemann-Pick disease, type C 2019-08-26 criteria provided, single submitter clinical testing Variant summary: NPC1 c.3591+1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 5' splicing donor site. At least one publication reports experimental evidence that this variant affects mRNA splicing resulting in an unstable protein from two possible transcripts (Ribeiro_2001). The variant allele was found at a frequency of 1.2e-05 in 249950 control chromosomes. c.3591+1G>A has been reported in the literature in individuals affected with Niemann-Pick Disease Type C (Ribeiro_2001, Park_2003, Stampfer_2013). These data indicate that the variant is likely to be associated with disease. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000003107 SCV000023265 pathogenic Niemann-Pick disease type C1 2001-07-01 no assertion criteria provided literature only

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