ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.3457G>A (p.Ala1153Thr)

gnomAD frequency: 0.00001  dbSNP: rs774812187
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001042871 SCV001206578 uncertain significance Hypertrophic cardiomyopathy 2021-09-25 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 1153 of the MYH7 protein (p.Ala1153Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. 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: 840785). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Ambry Genetics RCV002451164 SCV002617941 uncertain significance Cardiovascular phenotype 2020-11-16 criteria provided, single submitter clinical testing The p.A1153T variant (also known as c.3457G>A), located in coding exon 25 of the MYH7 gene, results from a G to A substitution at nucleotide position 3457. The alanine at codon 1153 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002505571 SCV002812086 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 2021-07-02 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004004759 SCV004824772 uncertain significance Cardiomyopathy 2023-12-18 criteria provided, single submitter clinical testing This missense variant replaces alanine with threonine at codon 1153 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 not been reported in individuals affected with MYH7-related disorders in the literature. This variant has been identified in 3/235768 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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