Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV001150614 | SCV001311695 | uncertain significance | Autosomal dominant nonsyndromic hearing loss 17 | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Illumina Laboratory Services, |
RCV001150615 | SCV001311696 | uncertain significance | MYH9-related disorder | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Invitae | RCV002559453 | SCV002949525 | likely benign | not provided | 2023-11-10 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002559454 | SCV003540607 | uncertain significance | Inborn genetic diseases | 2021-07-14 | criteria provided, single submitter | clinical testing | The c.5108G>A (p.R1703Q) alteration is located in exon 36 (coding exon 35) of the MYH9 gene. This alteration results from a G to A substitution at nucleotide position 5108, causing the arginine (R) at amino acid position 1703 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Neuberg Supratech Reference Laboratories Pvt Ltd, |
RCV003339517 | SCV004048505 | uncertain significance | Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss | criteria provided, single submitter | clinical testing | The c.5108G>A (p.Arg1703Gln) missense variant in MYH9 gene has been submitted to ClinVar as a Variant of Uncertain Significance (VUS). It has not been reported in affected individuals. The p.Arg1703Gln variant is reported with the allele frequency (0.001%) in the gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The amino acid Arg at position 1703 is changed to a Gln changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted to be damaging by both SIFT and PolyPhen2. The residue is conserved across species. The amino acid change p.Arg1703Gln in MYH9 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Variant of Uncertain Significance (VUS). |