ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.4097C>T (p.Ser1366Leu)

gnomAD frequency: 0.00004  dbSNP: rs767000995
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000802060 SCV000941873 uncertain significance Hypertrophic cardiomyopathy 2024-01-21 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1366 of the MYH7 protein (p.Ser1366Leu). This variant is present in population databases (rs767000995, gnomAD 0.006%). 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: 647534). 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.
Color Diagnostics, LLC DBA Color Health RCV001185407 SCV001351605 uncertain significance Cardiomyopathy 2022-10-20 criteria provided, single submitter clinical testing This missense variant replaces serine with leucine at codon 1366 of the MYH7 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with dilated cardiomyopathy (PMID: 31983221). This variant has been identified in 3/251468 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.
Ambry Genetics RCV002325544 SCV002628353 uncertain significance Cardiovascular phenotype 2024-08-14 criteria provided, single submitter clinical testing The p.S1366L variant (also known as c.4097C>T), located in coding exon 28 of the MYH7 gene, results from a C to T substitution at nucleotide position 4097. The serine at codon 1366 is replaced by leucine, an amino acid with dissimilar properties. This variant has been reported in individuals from dilated cardiomyopathy cohorts, but clinical details were limited (Ware JS et al. J Am Coll Cardiol, 2018 May;71:2293-2302; Mazzarotto F et al. Circulation, 2020 Feb;141:387-398). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002501075 SCV002812673 uncertain significance Hypertrophic cardiomyopathy 1; Myopathy, myosin storage, autosomal recessive; Myosin storage myopathy; Congenital myopathy with fiber type disproportion; Dilated cardiomyopathy 1S; MYH7-related skeletal myopathy 2021-08-10 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV001185407 SCV004814383 uncertain significance Cardiomyopathy 2024-07-20 criteria provided, single submitter clinical testing This missense variant replaces serine with leucine at codon 1366 of the MYH7 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with dilated cardiomyopathy (PMID: 31983221). This variant has been identified in 3/251468 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.

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