Submissions for variant NM_198253.3(TERT):c.2053G>A (p.Asp685Asn)

dbSNP: rs1579575848

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002535497	SCV000959849	likely pathogenic	Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis	2023-05-19	criteria provided, single submitter	clinical testing	In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 685 of the TERT protein (p.Asp685Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with TERT-related conditions (PMID: 32076714; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 661719). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TERT protein function.