Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000039048 | SCV000062726 | uncertain significance | not specified | 2012-12-11 | criteria provided, single submitter | clinical testing | The Thr219Met variant in MYO3A has not been reported in the literature nor previ ously identified by our laboratory. Computational analyses (biochemical amino ac id properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the Th r219Met variant may impact the protein, though this information is not predictiv e enough to determine pathogenicity. This variant has been identified in 0.04% (2/4406) of African American chromosomes in a broad population by the NHLBI Exom e sequencing project (http://evs.gs.washington.edu/EVS/). Although this variant has been seen in the general population, its frequency is not high enough to rul e out a pathogenic role. In summary, additional data is needed to determine the clinical significance of this variant. |
Fulgent Genetics, |
RCV000764887 | SCV000896047 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 30 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002513521 | SCV003486421 | uncertain significance | not provided | 2022-10-14 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with MYO3A-related conditions. This variant is present in population databases (rs377660409, gnomAD 0.05%). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 219 of the MYO3A protein (p.Thr219Met). ClinVar contains an entry for this variant (Variation ID: 45821). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. |
Ambry Genetics | RCV003352755 | SCV004052455 | uncertain significance | Inborn genetic diseases | 2023-08-15 | criteria provided, single submitter | clinical testing | The c.656C>T (p.T219M) alteration is located in exon 8 (coding exon 6) of the MYO3A gene. This alteration results from a C to T substitution at nucleotide position 656, causing the threonine (T) at amino acid position 219 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |