Submissions for variant NM_000256.3(MYBPC3):c.521_523del (p.Phe174del)

dbSNP: rs730880722

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000158486	SCV000208421	uncertain significance	not provided	2014-10-24	criteria provided, single submitter	clinical testing	The c.521_523delTCT variant in the MYBPC3 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. This variant results in an in-frame deletion of a Phenylalanine residue at codon 174, denoted p.Phe174del. Only a few in-frame deletions in the MYBPC3 gene have been reported in association with cardiomyopathy, indicating perhaps this region of the protein may be tolerant of change. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003748195	SCV004401417	uncertain significance	Hypertrophic cardiomyopathy	2024-04-29	criteria provided, single submitter	clinical testing	This variant, c.521_523del, results in the deletion of 1 amino acid(s) of the MYBPC3 protein (p.Phe174del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). 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: 181158). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
Ambry Genetics	RCV004984701	SCV005453714	uncertain significance	Cardiovascular phenotype	2024-11-25	criteria provided, single submitter	clinical testing	The c.521_523delTCT variant (also known as p.F174del) is located in coding exon 5 of the MYBPC3 gene. This variant results from an in-frame TCT deletion at nucleotide positions 521 to 523. This results in the in-frame deletion of a phenylalanine at codon 174. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Based on the available evidence, the clinical significance of this variant remains unclear.