Submissions for variant NM_000256.3(MYBPC3):c.3299A>T (p.Tyr1100Phe)

dbSNP: rs769925144

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001182667	SCV001348181	uncertain significance	Cardiomyopathy	2023-04-20	criteria provided, single submitter	clinical testing	This missense variant replaces tyrosine with phenylalanine at codon 1100 of the MYBPC3 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MYBPC3-related disorders in the literature. This variant has not been identified 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.
AiLife Diagnostics, AiLife Diagnostics	RCV002224003	SCV002502313	uncertain significance	not provided	2021-09-29	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV002224003	SCV002541136	uncertain significance	not provided	2021-12-23	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV003748326	SCV004506821	uncertain significance	Hypertrophic cardiomyopathy	2025-01-16	criteria provided, single submitter	clinical testing	This sequence change replaces tyrosine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 1100 of the MYBPC3 protein (p.Tyr1100Phe). 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: 922548). 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.
All of Us Research Program, National Institutes of Health	RCV003748326	SCV004836624	uncertain significance	Hypertrophic cardiomyopathy	2024-08-23	criteria provided, single submitter	clinical testing	This missense variant replaces tyrosine with phenylalanine at codon 1100 of the MYBPC3 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on protein structure and function. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified 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.