Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory of Molecular Genetics |
RCV000782008 | SCV000920469 | likely pathogenic | not provided | 2018-01-16 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV001334024 | SCV001526758 | likely pathogenic | Spinocerebellar ataxia type 15/16 | 2018-01-16 | criteria provided, single submitter | clinical testing | This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. |
| Genetic Services Laboratory, |
RCV000782008 | SCV002064356 | likely pathogenic | not provided | 2017-09-28 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004586923 | SCV005077388 | likely pathogenic | Spinocerebellar ataxia type 29 | 2024-04-05 | criteria provided, single submitter | clinical testing | Variant summary: ITPR1 c.742_744delGAG (p.Glu248del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant was absent in 248370 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.742_744delGAG in individuals affected with Spinocerebellar Ataxia 29 and no experimental evidence demonstrating its impact on protein function have been reported in the literature. The variant has been observed in an internal whole exome sequencing case where the variant was found in the proband and similarly affected sibling, however was found in the mother at an the allele ratio that is lower than would be expected which may be indciative of germline mosaicism inheritance. There are at least three reports of other germline mosaic missense variants in individuals affected with spinocerebellar ataxia and Gillespie syndrome (PMID: 37821226, 31632679, 35118825). ClinVar contains an entry for this variant (Variation ID: 633506). One ClinVar submitter has reported this variant to be inherited in a de novo manner. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Victorian Clinical Genetics Services, |
RCV004586923 | SCV005400156 | pathogenic | Spinocerebellar ataxia type 29 | 2023-07-17 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0103 - Loss of function and gain of function are known mechanisms of disease in this gene and are associated with spinocerebellar ataxia 29, congenital nonprogressive (MIM#117360). Missense variants have been reported to cause both loss and gain of function mechanisms (PMID:28620721, PMID:29925855, OMIM), while variants resulting in a truncated protein have been reported to cause loss of function only (PMID:29925855). (I) 0108 - This gene is associated with both recessive and dominant disease. There is no established genotype-phenotype correlation regarding the location of a variant and its mode of inheritance; however, only biallelic truncating variants have been reported for recessive disease (PMID:29925855). (I) 0213 - In-frame insertion/deletion in a non-repetitive region that has high conservation. (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0602 - Variant is located in a hotspot region or cluster of pathogenic variants (DECIPHER). (SP) 0705 - No comparable inframe variants have previous evidence for pathogenicity. (I) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. This variant has been reported once as a VUS (LOVD) and three times as likely pathogenic in a clinical testing laboratory, where in at least one case, de novo inheritance was observed (ClinVar). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed, by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |