ClinVar Miner

Submissions for variant NM_005529.7(HSPG2):c.9564G>C (p.Gln3188His)

gnomAD frequency: 0.00066  dbSNP: rs149644947
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000367014 SCV000354697 uncertain significance Lethal Kniest-like syndrome 2018-01-12 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.
Illumina Laboratory Services, Illumina RCV000274765 SCV000354698 uncertain significance Schwartz-Jampel syndrome 2018-01-12 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.
GeneDx RCV000414737 SCV000491983 uncertain significance not specified 2016-11-23 criteria provided, single submitter clinical testing The Q3188H variant in the HSPG2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. Although not present in the homozygous state, the NHLBI ESP Exome Sequencing Project reports Q3188H was observed in 11/8600 alleles (0.13%) from individuals of European ancestry, indicating it may be a rare variant in this population. The Q3188H variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution also occurs at a position that is conserved across mammalian species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret Q3188H as a variant of uncertain significance.
Athena Diagnostics Inc RCV000414737 SCV001475897 benign not specified 2020-02-26 criteria provided, single submitter clinical testing
Invitae RCV001348418 SCV001542721 likely benign not provided 2024-01-18 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001348418 SCV002049076 uncertain significance not provided 2021-09-09 criteria provided, single submitter clinical testing The HSPG2 c.9564G>C; p.Gln3188His variant (rs149644947), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 295756). It is observed in the Ashkenazi Jewish population at an overall frequency of 0.43% (45/10370 alleles) in the Genome Aggregation Database. The glutamine at codon 3188 is moderately conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.353). Due to limited evidence, the clinical significance of the p.Gln3188His variant is uncertain at this time.
Ambry Genetics RCV002522108 SCV003678421 likely benign Inborn genetic diseases 2021-11-03 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Revvity Omics, Revvity Omics RCV001348418 SCV003811329 uncertain significance not provided 2021-05-03 criteria provided, single submitter clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV001348418 SCV001798418 uncertain significance not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001348418 SCV001966407 uncertain significance not provided no assertion criteria provided clinical testing

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