ClinVar Miner

Submissions for variant NM_000512.5(GALNS):c.230C>G (p.Pro77Arg)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics RCV001062057 SCV001190349 likely pathogenic Mucopolysaccharidosis, MPS-IV-A criteria provided, single submitter clinical testing A Homozygous missense variation in exon 2 of the GALNS gene that results in the amino acid substitution of Arginine for Proline at codon 77 was detected. The observed variant c.230C>G (p.Pro77Arg) has not been reported in the 1000 genomes and ExAC databases. The in silico prediction of the variant is damaging by LRT and MutationTaster2. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as likely pathogenic.
Invitae RCV001062057 SCV001226829 pathogenic Mucopolysaccharidosis, MPS-IV-A 2019-03-26 criteria provided, single submitter clinical testing This sequence change replaces proline with arginine at codon 77 of the GALNS protein (p.Pro77Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with mucopolysaccharidosis type IVA (MPS IVA) (PMID: 7633425, 15235041, 23876334, Invitae) and to segregate with MPS IVA in a family (Invitae). This variant has been reported to affect GALNS protein function (PMID: 10814710). This variant disrupts the p.Pro77 amino acid residue in GALNS. Another variant that disrupt this residue has been observed in individuals with GALNS-related conditions (PMID: 25252036), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.

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