ClinVar Miner

Submissions for variant NM_000188.3(HK1):c.1370C>T (p.Thr457Met)

dbSNP: rs1057517928
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000413860 SCV000491089 likely pathogenic not provided 2016-05-17 criteria provided, single submitter clinical testing The T457M variant in the HK1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The T457M variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The T457M 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 that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. The T457M variant is a strong candidate for a pathogenic variant.
Fulgent Genetics, Fulgent Genetics RCV000763213 SCV000893839 likely pathogenic Charcot-Marie-Tooth disease type 4G; Hemolytic anemia due to hexokinase deficiency; Retinitis pigmentosa 79 2018-10-31 criteria provided, single submitter clinical testing
Institute Of Human Genetics Munich, Klinikum Rechts Der Isar, Tu München RCV000850129 SCV001149802 pathogenic Neurodevelopmental disorder with visual defects and brain anomalies 2020-02-06 criteria provided, single submitter clinical testing
Ambry Genetics RCV001266327 SCV001444501 likely pathogenic Inborn genetic diseases 2020-03-05 criteria provided, single submitter clinical testing The alteration results in an amino acid change: The c.1370C>T (p.T457M) alteration is located in coding exon 10 of the HK1 gene. This alteration results from a C to T substitution at nucleotide position 1370, causing the threonine (T) at amino acid position 457 to be replaced by a methionine (M). The alteration is not observed in population databases: Based on data from the Genome Aggregation Database (gnomAD), the HK1 c.1370C>T alteration was not observed, with coverage at this position. The alteratione has been observed in affected individuals: This alteration was described to occur de novo in three individuals from two families with neurodevelopmental abnormalities. Common features included developmental delay, brain MRI anomalies, and optic atrophy. Additional issues included seizures, tone abnormalities, failure to thrive, swallowing and feeding difficulties, hearing loss, and laryngotracheomalacia (Okur, 2019). The altered amino acid is conserved throughout evolution: The p.T457 amino acid is conserved in available vertebrate species. The alteration is predicted tolerated by in silico modeling: The p.T457M alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic.
CeGaT Center for Human Genetics Tuebingen RCV000413860 SCV001501992 pathogenic not provided 2020-08-01 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV000850129 SCV001950052 uncertain significance Neurodevelopmental disorder with visual defects and brain anomalies 2021-07-20 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000850129 SCV002765138 pathogenic Neurodevelopmental disorder with visual defects and brain anomalies 2022-12-20 criteria provided, single submitter clinical testing
Baylor Genetics RCV000850129 SCV003835364 pathogenic Neurodevelopmental disorder with visual defects and brain anomalies 2021-01-15 criteria provided, single submitter clinical testing
OMIM RCV000850129 SCV000992293 pathogenic Neurodevelopmental disorder with visual defects and brain anomalies 2019-08-22 no assertion criteria provided literature only

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