Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| New York Genome Center | RCV004799304 | SCV001431112 | uncertain significance | Neurodevelopmental disorder with visual defects and brain anomalies | 2019-11-12 | criteria provided, single submitter | clinical testing | This variant substitutes a moderately conserved Serine for Asparagine at amino acid 372/953 (coding exon:13/23). This variant is absent from gnomAD and ExAC, suggesting it is not a common benign variant in the populations represented in these databases. In silicoalgorithms do not agree on the effect of this variant, as itis predicted both Neutral (Provean; score: -0.38) and Damaging (SIFT; score: 0.031) to the function of the canonical transcript. To our current knowledge this variant has not been reported in affected individuals in the literature. The p.Ser372 variant is within the Hexokinase large subdomain 1, which is where several other pathogenic variants have been identified in individuals affected with autosomal dominant Neurodevelopmental disorder with visual defects and brain anomalies. |
| Labcorp Genetics |
RCV001343303 | SCV001537273 | uncertain significance | not provided | 2023-10-03 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 337 of the HK1 protein (p.Ser337Asn). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with HK1-related conditions. ClinVar contains an entry for this variant (Variation ID: 977389). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt HK1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV002570576 | SCV003716129 | uncertain significance | Inborn genetic diseases | 2021-10-12 | criteria provided, single submitter | clinical testing | The c.1010G>A (p.S337N) alteration is located in exon 8 (coding exon 8) of the HK1 gene. This alteration results from a G to A substitution at nucleotide position 1010, causing the serine (S) at amino acid position 337 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004800760 | SCV005423362 | uncertain significance | not specified | 2024-10-31 | criteria provided, single submitter | clinical testing | Variant summary: HK1 c.1010G>A (p.Ser337Asn) results in a conservative amino acid change located in the Hexokinase, C-terminal domain (IPR022673) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 251482 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1010G>A in individuals affected with Hemolytic anemia due to hexokinase deficiency and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 977389). Based on the evidence outlined above, the variant was classified as uncertain significance. |