ClinVar Miner

Submissions for variant NM_002471.3(MYH6):c.5293G>A (p.Ala1765Thr) (rs397516775)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000037529 SCV000061187 uncertain significance not specified 2012-01-24 criteria provided, single submitter clinical testing The Ala1765Thr variant (MYH6) has not been reported in the literature nor previo usly identified by our laboratory. Alanine (Ala) at position 1765 is conserved i n mammals and in evolutionarily distant species, but computational analyses (bio chemical amino acid properties, AlignGVGD, PolyPhen2, and SIFT) do not provide s trong support for or against an impact to the protein. Additional information is needed to fully assess the clinical significance of the Ala1765Thr variant.
Invitae RCV000467764 SCV000546145 uncertain significance Familial hypertrophic cardiomyopathy 14 2018-08-01 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 1765 of the MYH6 protein (p.Ala1765Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs397516775, ExAC 0.01%) but has not been reported in the literature in individuals with a MYH6-related disease. ClinVar contains an entry for this variant (Variation ID: 44533). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. Because it is found in the population at an appreciable frequency, this variant is not anticipated to cause disease. However, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000619201 SCV000735750 uncertain significance Cardiovascular phenotype 2017-02-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000770426 SCV000901869 uncertain significance Cardiomyopathy 2017-01-04 criteria provided, single submitter clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000845414 SCV000987482 uncertain significance Primary familial hypertrophic cardiomyopathy criteria provided, single submitter clinical testing

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