ClinVar Miner

Submissions for variant NM_022356.4(P3H1):c.1383_1389dup (p.Lys464fs)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics RCV002286562 SCV002574911 pathogenic Osteogenesis imperfecta type 8 2022-07-22 criteria provided, single submitter clinical testing A Homozygous variation in exon 9 of the P3H1gene that results in the amino acid substitution of Glutamic acid for Lysin at codon 464 was detected. The observed variant c.1383_1389dup (p.Lys464GlufsTer19) has not been reported in the 1000 genomes and databases. The in silico prediction of the variant are possibly damaging by MutationTaster2. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as pathogenic.
Neuberg Centre For Genomic Medicine, NCGM RCV002286562 SCV004101535 pathogenic Osteogenesis imperfecta type 8 2023-07-22 criteria provided, single submitter clinical testing The observed frameshift c.1383_1389dup p.Lys464GlufsTer19 variant in P3H1 gene has been previously reported in homozygous state in multiple individuals affected with Osteogenesis imperfecta Pepin MG et al. 2013; Marini JC et al. 2010; Baldridge D et al. 2008. The p.Lys464GlufsTer19 variant is absent in gnomAD Exomes. This variant has been submitted to the ClinVar database as Pathogenic. This variant causes a frameshift starting with codon Lysine 464, changes this amino acid to Glutamic Acid residue, and creates a premature Stop codon at position 19 of the new reading frame, denoted p.Lys464GlufsTer19. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab RCV002286562 SCV004177658 likely pathogenic Osteogenesis imperfecta type 8 2023-04-11 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002286562 SCV004279257 pathogenic Osteogenesis imperfecta type 8 2024-07-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys464Glufs*19) in the P3H1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in P3H1 are known to be pathogenic (PMID: 17277775, 18566967, 19088120, 22281939). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with osteogenesis imperfecta (PMID: 18566967, 27383115). ClinVar contains an entry for this variant (Variation ID: 1707605). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002286562 SCV005647493 pathogenic Osteogenesis imperfecta type 8 2024-06-21 criteria provided, single submitter clinical testing

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