Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV003268456 | SCV003983384 | uncertain significance | Inborn genetic diseases | 2023-05-22 | criteria provided, single submitter | clinical testing | The c.2951T>C (p.L984P) alteration is located in exon 22 (coding exon 22) of the SNRNP200 gene. This alteration results from a T to C substitution at nucleotide position 2951, causing the leucine (L) at amino acid position 984 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Victorian Clinical Genetics Services, |
RCV004786913 | SCV005398161 | uncertain significance | Retinitis pigmentosa 33 | 2022-03-31 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3B. Following criteria are met: 0105 - The mechanism of disease for this gene is not clearly established. Both loss-of-function and gain-of-function have been suggested, based on different functions of the protein (PMID: 19878916, 24302620). (I) 0108 - This gene is associated with both recessive and dominant disease. However, no clear genotype-phenotype correlation has been established (PMID: 31260034). (I) 0200 - Variant is predicted to result in a missense amino acid change from leucine to proline. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 (v3: 1 heterozygote, 0 homozygotes). (SP) 0309 - Multiple alternative amino acid changes at the same position have been observed in gnomAD (highest allele count: 3 heterozygotes, 0 homozygotes). (I) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0600 - Variant is located in the annotated Sec 63 domain (DECIPHER). (I) 0710 - Another missense variant comparable to the one identified in this case has inconclusive previous evidence for pathogenicity. p.(Leu984Gln), which has a higher grantham score than our variant, has been reported as a VUS, however no further evidence was provided (LOVD). (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |