Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV003220053 | SCV003908736 | uncertain significance | Inborn genetic diseases | 2023-02-27 | criteria provided, single submitter | clinical testing | The c.3323A>C (p.E1108A) alteration is located in exon 26 (coding exon 25) of the MYH9 gene. This alteration results from a A to C substitution at nucleotide position 3323, causing the glutamic acid (E) at amino acid position 1108 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV003720802 | SCV004503870 | uncertain significance | not provided | 2024-01-17 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 1108 of the MYH9 protein (p.Glu1108Ala). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with MYH9-related conditions. ClinVar contains an entry for this variant (Variation ID: 2489820). 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 MYH9 protein function with a negative predictive value of 80%. 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. |
Prevention |
RCV004725683 | SCV005337258 | uncertain significance | MYH9-related disorder | 2024-05-09 | no assertion criteria provided | clinical testing | The MYH9 c.3323A>C variant is predicted to result in the amino acid substitution p.Glu1108Ala. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0033% of alleles in individuals of South Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |