Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV004302017 | SCV003956100 | uncertain significance | not specified | 2023-05-17 | criteria provided, single submitter | clinical testing | The c.1374G>C (p.K458N) alteration is located in exon 17 (coding exon 15) of the MYH7B gene. This alteration results from a G to C substitution at nucleotide position 1374, causing the lysine (K) at amino acid position 458 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV003738410 | SCV004558058 | uncertain significance | not provided | 2024-01-29 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 458 of the MYH7B protein (p.Lys458Asn). This variant is present in population databases (rs757932346, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with MYH7B-related conditions. ClinVar contains an entry for this variant (Variation ID: 2523179). 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 expected to disrupt MYH7B protein function with a positive 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. |