ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.3557G>A (p.Arg1186His) (rs200444084)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000479463 SCV000339684 likely pathogenic not provided 2016-03-30 criteria provided, single submitter clinical testing
GeneDx RCV000479463 SCV000568739 pathogenic not provided 2017-02-24 criteria provided, single submitter clinical testing The R1186H variant in the NPC1 gene has been reported previously in association with Niemann-Pick disease type C (NPC) when present in the homozygous state or with another disease causing variant (Carstea et al., 1997; Sztolsztener et al., 2010; Jahnova et al., 2014). The R1186H 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). The R1186H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (A1187G, A1187V, E1189G, L1191F) have been reported in the Human Gene Mutation Database in association with NPC (Stenson et al., 2014), supporting the functional importance of this region of the protein. We interpret R1186H as a pathogenic variant.
Counsyl RCV000169602 SCV000221121 pathogenic Niemann-Pick disease type C1 2018-12-21 no assertion criteria provided clinical testing

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