ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.166G>A (p.Gly56Ser)

gnomAD frequency: 0.00001  dbSNP: rs397515918
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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, Mass General Brigham Personalized Medicine RCV000035425 SCV000059073 likely benign not specified 2014-11-12 criteria provided, single submitter clinical testing p.Gly56Ser in exon 2 of MYBPC3: This variant is not expected to have clinical si gnificance due to a lack of conservation across species, including mammals. Of n ote, 10 mammals have a serine (Ser) at this position despite high nearby amino a cid conservation. In addition, the change to serine (Ser) was predicted to be be nign using a computational tool clinically validated by our laboratory. This too l's benign prediction is estimated to be correct 89% of the time (Jordan 2011).
Labcorp Genetics (formerly Invitae), Labcorp RCV000472025 SCV000546486 uncertain significance Hypertrophic cardiomyopathy 2024-12-04 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 56 of the MYBPC3 protein (p.Gly56Ser). 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 missense change has been observed in individuals with dilated cardiomyopathy (PMID: 27532257). ClinVar contains an entry for this variant (Variation ID: 42558). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Color Diagnostics, LLC DBA Color Health RCV001190895 SCV001358530 likely benign Cardiomyopathy 2018-12-10 criteria provided, single submitter clinical testing
GeneDx RCV001536271 SCV001753004 uncertain significance not provided 2023-08-23 criteria provided, single submitter clinical testing Reported in at least one individual with DCM (Pugh et al., 2014); however, specific clinical information was not provided; In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 24503780, 28679633, 27532257)
Ambry Genetics RCV004017287 SCV004849148 uncertain significance Cardiovascular phenotype 2019-04-18 criteria provided, single submitter clinical testing The c.166G>A (p.G56S) alteration is located in exon 2 (coding exon 2) of the MYBPC3 gene. This alteration results from a G to A substitution at nucleotide position 166, causing the glycine (G) at amino acid position 56 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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