ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.410C>T (p.Thr137Met) (rs372947142)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522597 SCV000617719 uncertain significance not provided 2017-07-10 criteria provided, single submitter clinical testing The T137M variant in the NPC1 gene has been reported previously in association with Niemann-Pick disease type C, when present in the homozygous state or when seen with another variant, however, some patients have been reported to have normal biochemical studies (Sun et al., 2001; Fernandez-Valero et al., 2005; Garver et al., 2010; Akizu et al., 2013). Additionally, functional studies showed T137M exhibits normal binding to both 25-hydroxycholesterol and cholesterol (Infante et al., 2008). The T137M 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 T137M variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position where amino acids with similar properties to Threonine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret T137M as a variant of uncertain significance.
Counsyl RCV000674009 SCV000799278 likely pathogenic Niemann-Pick disease type C1 2018-04-09 criteria provided, single submitter clinical testing
Baylor Genetics RCV000674009 SCV001163441 pathogenic Niemann-Pick disease type C1 criteria provided, single submitter clinical testing

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