ClinVar Miner

Submissions for variant NM_001130144.3(LTBP3):c.2417C>T (p.Ser806Phe)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003832727 SCV004630180 uncertain significance Brachyolmia-amelogenesis imperfecta syndrome 2024-01-28 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 806 of the LTBP3 protein (p.Ser806Phe). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with LTBP3-related conditions. 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.
Molecular Genetics, Royal Melbourne Hospital RCV003994593 SCV004812697 uncertain significance Geleophysic dysplasia 2023-03-30 criteria provided, single submitter clinical testing This sequence change in LTBP3 is predicted to replace serine with phenylalanine at codon 806, p.(Ser806Phe). The serine residue is highly conserved (100 vertebrates, UCSC), and is located in the EGF-like calcium binding domain 7. There is a large physicochemical difference between serine and phenylalanine. The highest population minor allele frequency in the population database gnomAD v3.1 is 0.02% (3/15,280 alleles) in the Latino/admixed American population. To our knowledge, this variant has not been reported in the literature in any individuals. Multiple lines of computational evidence predict a deleterious effect for the missense substitution (6/6 algorithms). Based on the classification scheme RMH Modified ACMG Guidelines v1.5.1, this variant is classified as a VARIANT OF UNCERTAIN SIGNIFICANCE. Following criteria are met: PP3.

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