Submissions for variant NM_001130144.3(LTBP3):c.3839_3840delinsAA (p.Phe1280Ter)

dbSNP: rs2496108954

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002639552	SCV002972718	uncertain significance	Brachyolmia-amelogenesis imperfecta syndrome	2022-07-19	criteria provided, single submitter	clinical testing	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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with LTBP3-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.3%). This sequence change creates a premature translational stop signal (p.Phe1280*) in the LTBP3 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 24 amino acid(s) of the LTBP3 protein.
PreventionGenetics, part of Exact Sciences	RCV003961101	SCV004784568	uncertain significance	LTBP3-related disorder	2024-01-17	no assertion criteria provided	clinical testing	The LTBP3 c.3839_3840delinsAA variant is predicted to result in premature protein termination (p.Phe1280*). To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. While loss of function variants have been reported as causative in LTBP3, few such variants have been reported downstream of this variant. Therefore, it is unclear if this variant impacts protein function. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.