ClinVar Miner

Submissions for variant NM_005529.7(HSPG2):c.662G>A (p.Arg221Gln)

gnomAD frequency: 0.00003  dbSNP: rs539990898
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV000992146 SCV001144180 uncertain significance not provided 2019-06-17 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001002574 SCV001160547 uncertain significance not specified 2019-05-03 criteria provided, single submitter clinical testing The HSPG2 c.662G>A; p.Arg221Gln variant (rs539990898), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is found in the Finnish European population with an allele frequency of 0.036% (9/25098 alleles) in the Genome Aggregation Database. The arginine at codon 221 is weakly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. Due to limited information, the clinical significance of the p.Arg221Gln variant is uncertain at this time.
Labcorp Genetics (formerly Invitae), Labcorp RCV000992146 SCV002166622 uncertain significance not provided 2022-06-05 criteria provided, single submitter clinical testing 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. This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 221 of the HSPG2 protein (p.Arg221Gln). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 804909). This variant has not been reported in the literature in individuals affected with HSPG2-related conditions. This variant is present in population databases (rs539990898, gnomAD 0.04%). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site.
Ambry Genetics RCV002549780 SCV003545306 uncertain significance Inborn genetic diseases 2024-01-03 criteria provided, single submitter clinical testing The c.662G>A (p.R221Q) alteration is located in exon 6 (coding exon 6) of the HSPG2 gene. This alteration results from a G to A substitution at nucleotide position 662, causing the arginine (R) at amino acid position 221 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV000992146 SCV005373013 uncertain significance not provided 2023-07-11 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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