Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001230513 | SCV001402994 | uncertain significance | Joubert syndrome 21 | 2022-09-07 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 121 of the CSPP1 protein (p.His121Arg). This variant is present in population databases (rs370605967, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with CSPP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 957521). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
Ambry Genetics | RCV003246781 | SCV003951473 | uncertain significance | Inborn genetic diseases | 2023-04-06 | criteria provided, single submitter | clinical testing | The c.362A>G (p.H121R) alteration is located in exon 4 (coding exon 4) of the CSPP1 gene. This alteration results from a A to G substitution at nucleotide position 362, causing the histidine (H) at amino acid position 121 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |