ClinVar Miner

Submissions for variant NM_005529.7(HSPG2):c.764C>T (p.Pro255Leu)

gnomAD frequency: 0.00005  dbSNP: rs369712921
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center RCV001280788 SCV001468114 uncertain significance not provided 2020-10-01 criteria provided, single submitter clinical testing
GeneDx RCV001280788 SCV001999410 uncertain significance not provided 2021-01-18 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In-silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Has not been previously published as pathogenic or benign to our knowledge
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001280788 SCV002048226 uncertain significance not provided 2021-09-09 criteria provided, single submitter clinical testing The HSPG2 c.764C>T; p.Pro255Leu variant (rs369712921), to our knowledge, is not reported in the medical literature but it reported in ClinVar (Variation ID: 992351). It is observed in the Latino/Admixed American population at an overall frequency of 0.01% (5/34550 alleles) in the Genome Aggregation Database. The proline at codon 255 is weakly conserved, and computational analyses predict that this variant is neutral (REVEL: 0.122). Due to limited evidence, the clinical significance of the p.Pro255Leu variant is uncertain at this time.
Labcorp Genetics (formerly Invitae), Labcorp RCV001280788 SCV002200675 uncertain significance not provided 2024-12-02 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 255 of the HSPG2 protein (p.Pro255Leu). This variant is present in population databases (rs369712921, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with HSPG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 992351). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.
Revvity Omics, Revvity RCV001280788 SCV003811320 uncertain significance not provided 2019-07-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV003294182 SCV004000215 uncertain significance Inborn genetic diseases 2023-03-23 criteria provided, single submitter clinical testing The c.764C>T (p.P255L) alteration is located in exon 7 (coding exon 7) of the HSPG2 gene. This alteration results from a C to T substitution at nucleotide position 764, causing the proline (P) at amino acid position 255 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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