Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
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, |
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, |
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. |
Ce |
RCV000413860 | SCV001501992 | pathogenic | not provided | 2020-08-01 | criteria provided, single submitter | clinical testing | |
Institute of Human Genetics, |
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, |
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 |