ClinVar Miner

Submissions for variant NM_003922.4(HERC1):c.13843C>A (p.Leu4615Ile)

gnomAD frequency: 0.00002  dbSNP: rs759412132
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001776986 SCV002014020 uncertain significance not provided 2025-01-15 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001776986 SCV003024320 uncertain significance not provided 2022-07-02 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 4615 of the HERC1 protein (p.Leu4615Ile). 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1321007). This variant has not been reported in the literature in individuals affected with HERC1-related conditions. This variant is present in population databases (rs759412132, gnomAD 0.006%).
Ambry Genetics RCV004040784 SCV004881291 uncertain significance Inborn genetic diseases 2023-12-21 criteria provided, single submitter clinical testing The c.13843C>A (p.L4615I) alteration is located in exon 75 (coding exon 74) of the HERC1 gene. This alteration results from a C to A substitution at nucleotide position 13843, causing the leucine (L) at amino acid position 4615 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.