Submissions for variant NM_000512.5(GALNS):c.211A>G (p.Asn71Asp)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003104685	SCV003781537	uncertain significance	Mucopolysaccharidosis, MPS-IV-A	2022-04-12	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 71 of the GALNS protein (p.Asn71Asp). This variant is present in population databases (rs780624145, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with GALNS-related conditions. 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 not expected to disrupt GALNS protein function. 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	RCV004621750	SCV005119820	uncertain significance	Inborn genetic diseases	2024-04-22	criteria provided, single submitter	clinical testing	The c.211A>G (p.N71D) alteration is located in exon 2 (coding exon 2) of the GALNS gene. This alteration results from a A to G substitution at nucleotide position 211, causing the asparagine (N) at amino acid position 71 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.