Submissions for variant NM_198253.3(TERT):c.1571C>A (p.Pro524Gln)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003795137	SCV004590078	uncertain significance	Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis	2023-08-29	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 524 of the TERT protein (p.Pro524Gln). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TERT-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.
Ambry Genetics	RCV004559011	SCV005049058	uncertain significance	Dyskeratosis congenita	2023-07-03	criteria provided, single submitter	clinical testing	The p.P524Q variant (also known as c.1571C>A), located in coding exon 2 of the TERT gene, results from a C to A substitution at nucleotide position 1571. The proline at codon 524 is replaced by glutamine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.