ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.2198G>A (p.Arg733His) (rs534345197)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000770336 SCV000901770 uncertain significance Cardiomyopathy 2017-03-03 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000611582 SCV000733044 uncertain significance Familial hypertrophic cardiomyopathy 4 no assertion criteria provided clinical testing
GeneDx RCV000158442 SCV000208377 uncertain significance not provided 2019-01-14 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the MYBPC3 gene. The R733H variant has previously been reported in one individual with HCM who also harbored a variant in the TNNT2 gene (Garcia-Castro et al., 2009). Familial testing also identified the R733H variant in four apparently unaffected relatives, two of whom also harbored the TNNT2 variant. The other affected individual in this family had a mild HCM phenotype and only harbored the variant in the TNNT2 gene (Garcia-Castro et al., 2009). Nevertheless, the R733H variant was not observed in approximately 6,300 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. However, the R733H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Arginine are tolerated across species, and Histidine is the wild-type amino acid at this position in multiple species. Furthermore, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign.
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000611582 SCV000743556 uncertain significance Familial hypertrophic cardiomyopathy 4 2016-03-03 criteria provided, single submitter clinical testing

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