ClinVar Miner

Submissions for variant NM_152419.3(HGSNAT):c.1445T>A (p.Met482Lys) (rs121908284)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001378638 SCV001576254 likely pathogenic Mucopolysaccharidosis, MPS-III-C; Retinitis pigmentosa 73 2020-08-23 criteria provided, single submitter clinical testing This sequence change replaces methionine with lysine at codon 482 of the HGSNAT protein (p.Met482Lys). The methionine residue is moderately conserved and there is a moderate physicochemical difference between methionine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) withmucopolysaccharidosis type IIIC (PMID: 17033958). This variant is also known as c.1529T>A, p.M510K. ClinVar contains an entry for this variant (Variation ID: 1234). 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 HGSNAT protein function. Experimental studies have shown that this variant affects HGSNAT protein function (PMID: 19823584, 20583299). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
OMIM RCV000001293 SCV000021443 pathogenic Mucopolysaccharidosis, MPS-III-C 2006-11-01 no assertion criteria provided literature only

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