Submissions for variant NM_000257.4(MYH7):c.4489A>T (p.Thr1497Ser)

gnomAD frequency: 0.00001  dbSNP: rs928227757

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001348776	SCV001543091	uncertain significance	Hypertrophic cardiomyopathy	2024-03-02	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 1497 of the MYH7 protein (p.Thr1497Ser). 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 MYH7-related conditions. ClinVar contains an entry for this variant (Variation ID: 973032). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MYH7 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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001799055	SCV002042682	uncertain significance	Cardiomyopathy	2019-06-24	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV001799055	SCV004841331	uncertain significance	Cardiomyopathy	2023-10-23	criteria provided, single submitter	clinical testing	This missense variant replaces threonine with serine at codon 1497 of the MYH7 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MYH7-related disorders in the literature. This variant has been identified in 3/282848 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
GenomeConnect, ClinGen	RCV001249370	SCV001423361	not provided	not provided		no assertion provided	phenotyping only	Variant interpretted as Uncertain significance and reported on 07-22-2019 by Lab or GTR ID Credit Valley Hospital Department of Laboratory Medicine. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.