ClinVar Miner

Submissions for variant NM_003545.4(H4C5):c.136C>T (p.Arg46Cys)

dbSNP: rs950721550
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000998549 SCV001154679 uncertain significance not provided 2018-09-01 criteria provided, single submitter clinical testing
Genetics Laboratory, UDIAT-Centre Diagnòstic, Hospital Universitari Parc Tauli RCV001420269 SCV001622689 likely pathogenic See cases 2021-04-26 criteria provided, single submitter clinical testing PM2_supporting;PM6_moderate;PP3_supporting;PP5_supporting;BP1_supporting
Ambry Genetics RCV003346251 SCV004067378 pathogenic Inborn genetic diseases 2023-07-13 criteria provided, single submitter clinical testing The c.136C>T (p.R46C) alteration is located in exon 1 (coding exon 1) of the HIST1H4E gene. This alteration results from a C to T substitution at nucleotide position 136, causing the arginine (R) at amino acid position 46 to be replaced by a cysteine (C). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant has been determined to be the result of a de novo mutation in multiple individuals with features consistent with H4C5-related Tessadori-van Haaften neurodevelopmental syndrome (Tessadori, 2022). This amino acid position is highly conserved in available vertebrate species. This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000998549 SCV001798535 uncertain significance not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000998549 SCV001808124 uncertain significance not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000998549 SCV001968407 uncertain significance not provided no assertion criteria provided clinical testing
OMIM RCV003152614 SCV003841062 pathogenic Tessadori-Van Haaften neurodevelopmental syndrome 3 2023-01-20 no assertion criteria provided literature only

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