ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.3143G>A (p.Arg1048His)

gnomAD frequency: 0.00002  dbSNP: rs769018051
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001178569 SCV001343040 uncertain significance Cardiomyopathy 2023-11-01 criteria provided, single submitter clinical testing This missense variant replaces arginine with histidine at codon 1048 of the MYBPC3 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.4, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 6/241696 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.
Petrovsky National Research Centre of Surgery, The Federal Agency for Scientific Organizations RCV001264388 SCV001441572 uncertain significance Concentric hypertrophic cardiomyopathy; Left ventricular noncompaction cardiomyopathy 2020-10-16 criteria provided, single submitter clinical testing We observed a c.3143G>A (p.R1048H) genetic variant in a 44-y.o. female proband, diagnosed with left ventricular non-compaction and significant concentric hypertrophic cardiomyopathy. The frequency of the p.R1048H genetic variant according in gnomAD database is 2.482e-5. According to the online bioinformatic resources the p.R1048H genetic variant is probably pathogenic. However, in the absebse of familial screening (no family members were available) and functional studies we can classify the p.R1048H genetic variant as the variant with uncertain clinical significance.
Invitae RCV001370835 SCV001567377 uncertain significance Hypertrophic cardiomyopathy 2023-12-29 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1048 of the MYBPC3 protein (p.Arg1048His). This variant is present in population databases (rs769018051, gnomAD 0.006%). This missense change has been observed in individual(s) with clinical features of dilated cardiomyopathy (Invitae). ClinVar contains an entry for this variant (Variation ID: 188576). 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 tolerated. 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.
Fulgent Genetics, Fulgent Genetics RCV002485049 SCV002785430 uncertain significance Hypertrophic cardiomyopathy 4; Left ventricular noncompaction 10 2021-07-22 criteria provided, single submitter clinical testing

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