Submissions for variant NM_001082486.2(ACD):c.1306C>T (p.Pro436Ser)

dbSNP: rs201926842

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000652835	SCV000774707	uncertain significance	Dyskeratosis congenita, autosomal dominant 6	2017-09-24	criteria provided, single submitter	clinical testing	Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C25". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with ACD-related disease. This variant is present in population databases (rs201926842, ExAC 0.01%). This sequence change replaces proline with serine at codon 522 of the ACD protein (p.Pro522Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. 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.