Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV005809467 | SCV006500260 | uncertain significance | not specified | 2025-08-21 | criteria provided, single submitter | clinical testing | The c.1188C>G (p.I396M) alteration is located in exon 4 (coding exon 4) of the DCLRE1B gene. This alteration results from a C to G substitution at nucleotide position 1188, causing the isoleucine (I) at amino acid position 396 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001216754 | SCV001388566 | uncertain significance | Hoyeraal-Hreidarsson syndrome; Autosomal recessive dyskeratosis congenita | 2019-07-03 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This sequence change replaces isoleucine with methionine at codon 396 of the DCLRE1B protein (p.Ile396Met). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and methionine. This variant is present in population databases (rs769393520, ExAC 0.03%). This variant has not been reported in the literature in individuals with DCLRE1B-related conditions. |