Submissions for variant NM_024312.5(GNPTAB):c.3571C>T (p.Arg1191Cys)

gnomAD frequency: 0.00001  dbSNP: rs1481471124

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000673576	SCV000798794	uncertain significance	Mucolipidosis type II; Pseudo-Hurler polydystrophy	2018-04-03	criteria provided, single submitter	clinical testing
Invitae	RCV000673576	SCV001558578	likely pathogenic	Mucolipidosis type II; Pseudo-Hurler polydystrophy	2023-09-08	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 557433). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1191 of the GNPTAB protein (p.Arg1191Cys). This variant is present in population databases (no rsID available, gnomAD 0.004%). This missense change has been observed in individual(s) with mucolipidosis II (PMID: 29966168). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. 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 GNPTAB protein function. 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.
Natera, Inc.	RCV001830458	SCV002088561	uncertain significance	Mucolipidosis type II	2020-04-27	no assertion criteria provided	clinical testing
Department of Genetics and Endocrinology, Guangzhou Women and Children’s Medical Center	RCV003984845	SCV004041870	pathogenic	Mucolipidosis		no assertion criteria provided	clinical testing