ClinVar Miner

Submissions for variant NM_001142864.4(PIEZO1):c.6380C>T (p.Thr2127Met) (rs587776991)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000049236 SCV000967724 likely pathogenic Xerocytosis 2018-02-19 criteria provided, single submitter clinical testing The p.Thr2127Met variant in PIEZO1 has been reported in two individuals with cli nical features of dehydrated hereditary stomatocytosis (Andolfo 2013, Albuisson 2013). The variant cosegregated with disease in one family in 16 relatives over three generations, including 4 obligate carriers (Andolfo 2013). This variant ha s been identified in 1/838 Latino chromosomes and 1/3490 Finnish chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs587776991). In vitro functional studies provide some evidence that the p.Thr2 127Met variant may impact protein function by delaying inactivation time and the refore increasing cation transport (Albuisson 2103); however, these types of ass ays may not accurately represent biological function. In summary, although addit ional studies are required to fully establish its clinical significance, the p.T hr2127Met variant is likely pathogenic for dehydrated hereditary stomatocytosis in an autosomal dominant manner. ACMG/AMP Criteria applied: PP1_Strong; PM2; PS3 _Supporting
OMIM RCV000049236 SCV000077489 pathogenic Xerocytosis 2013-05-09 no assertion criteria provided literature only

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