Submissions for variant NM_001166114.2(PNPLA6):c.1292A>G (p.Tyr431Cys)

dbSNP: rs373050796

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001061063	SCV001225790	uncertain significance	Hereditary spastic paraplegia 39	2023-06-13	criteria provided, single submitter	clinical testing	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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PNPLA6 protein function. ClinVar contains an entry for this variant (Variation ID: 855736). This variant has not been reported in the literature in individuals affected with PNPLA6-related conditions. This variant is present in population databases (rs373050796, gnomAD 0.0009%). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 392 of the PNPLA6 protein (p.Tyr392Cys). 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.