Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Baylor Genetics | RCV001334192 | SCV001526972 | uncertain significance | Macrocephaly, dysmorphic facies, and psychomotor retardation | 2018-06-16 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
Labcorp Genetics |
RCV002547321 | SCV003280617 | uncertain significance | not provided | 2022-04-11 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with HERC1-related conditions. 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: "Benign"; Align-GVGD: "Class C65"). ClinVar contains an entry for this variant (Variation ID: 1032166). This variant is present in population databases (rs376280658, gnomAD 0.06%). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 1192 of the HERC1 protein (p.Cys1192Arg). |
Ambry Genetics | RCV002547322 | SCV003673021 | uncertain significance | Inborn genetic diseases | 2022-10-13 | criteria provided, single submitter | clinical testing | The c.3574T>C (p.C1192R) alteration is located in exon 19 (coding exon 18) of the HERC1 gene. This alteration results from a T to C substitution at nucleotide position 3574, causing the cysteine (C) at amino acid position 1192 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Prevention |
RCV003416223 | SCV004116882 | uncertain significance | HERC1-related disorder | 2023-02-20 | criteria provided, single submitter | clinical testing | The HERC1 c.3574T>C variant is predicted to result in the amino acid substitution p.Cys1192Arg. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.057% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/15-64015549-A-G). While we suspect this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |