ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.2162C>T (p.Thr721Ile)

dbSNP: rs1293844338
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000820641 SCV000961361 uncertain significance Hypertrophic cardiomyopathy 2023-12-30 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 721 of the MYBPC3 protein (p.Thr721Ile). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with MYBPC3-related conditions. ClinVar contains an entry for this variant (Variation ID: 662896). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Petrovsky National Research Centre of Surgery, The Federal Agency for Scientific Organizations RCV001267643 SCV001443818 uncertain significance See cases 2020-11-18 criteria provided, single submitter clinical testing We observed a genetic variant c.2162C>T (p.T721I) in MYBPC3 gene in a male 5 month proband diagnosed with left ventricular non-compaction and dilatation of cardiac chambers. The p.T721I genetic variant is present in gnomAD database with frequency of 4.076e-6, thus being rare. Online in silico tools predict the p.T721I genetic variant to be probably pathogenic. However, in the absence of functional studies and/or segregation analysis we could only classify the p.T721I genetic variant as a variant of uncertain clinical significance.
GeneDx RCV002462185 SCV002757379 uncertain significance not provided 2022-05-23 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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