Submissions for variant NM_000199.5(SGSH):c.808T>C (p.Phe270Leu)

gnomAD frequency: 0.00003  dbSNP: rs570170198

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000694738	SCV000823196	uncertain significance	Mucopolysaccharidosis, MPS-III-A	2022-09-13	criteria provided, single submitter	clinical testing	This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 270 of the SGSH protein (p.Phe270Leu). This variant is present in population databases (rs570170198, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SGSH-related conditions. ClinVar contains an entry for this variant (Variation ID: 573148). 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 SGSH 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.
Illumina Laboratory Services, Illumina	RCV000694738	SCV001283026	uncertain significance	Mucopolysaccharidosis, MPS-III-A	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Genome-Nilou Lab	RCV000694738	SCV002045159	uncertain significance	Mucopolysaccharidosis, MPS-III-A	2021-11-07	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000694738	SCV002788528	uncertain significance	Mucopolysaccharidosis, MPS-III-A	2022-02-10	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528627	SCV001740651	uncertain significance	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001528627	SCV001798714	uncertain significance	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV000694738	SCV002095128	uncertain significance	Mucopolysaccharidosis, MPS-III-A	2019-11-11	no assertion criteria provided	clinical testing