ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.964T>A (p.Ser322Thr) (rs730880859)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000158773 SCV000208708 likely pathogenic not provided 2012-09-27 criteria provided, single submitter clinical testing p.Ser322Thr (TCC>ACC):c.964 T>A in exon 11 of the MYH7 gene (NM_000257.2). The Ser322Thr variant in the MYH7 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Ser322Thr results in a conservative amino acid substitution of one neutral, polar residue for another at a position that is conserved through mammals. A mutation affecting the same residue (Ser322Phe), as well as mutations in nearby residues (Val320Met, Ala326Pro) have been reported in association with HCM, further supporting the functional importance of this region of the protein. Furthermore, the NHLBI ESP Exome Variant Server reports Ser322Thr was not observed in approximately 6,500 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. In summary, while Ser322Thr is a good candidate for a disease-causing mutation, with the clinical and molecular information available at this time we cannot unequivocally determine the clinical significance of this variant. The variant is found in HCM panel(s).
Invitae RCV000628973 SCV000749883 uncertain significance Hypertrophic cardiomyopathy 2017-10-10 criteria provided, single submitter clinical testing This sequence change replaces serine with threonine at codon 322 of the MYH7 protein (p.Ser322Thr). The serine residue is highly conserved and there is a small physicochemical difference between serine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with hypertrophic cardiomyopathy (PMID: 27532257). ClinVar contains an entry for this variant (Variation ID: 181330). A computational algorithm designed to assess the pathogenicity of variants in MYH7 with regard to hypertrophic cardiomyopathy predicted this sequence change to be tolerated. The algorithm has a sensitivity of 94% and a specificity of 89% (PMID: 21310275). This variant is found within a region of MYH7 between codons 181 and 937 that contains the majority of the myosin head domain. Missense variants in this region have been shown to be significantly overrepresented in individuals with hypertrophic cardiomyopathy (PMID: 27532257). 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.