Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000671518 | SCV000796502 | likely pathogenic | Alstrom syndrome | 2017-12-27 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000671518 | SCV001233884 | pathogenic | Alstrom syndrome | 2024-01-16 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Thr400Lysfs*11) in the ALMS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ALMS1 are known to be pathogenic (PMID: 17594715). This variant is present in population databases (rs761292021, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with ALMS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 555656). For these reasons, this variant has been classified as Pathogenic. |
Blueprint Genetics | RCV001074661 | SCV001240253 | pathogenic | Retinal dystrophy | 2019-02-22 | criteria provided, single submitter | clinical testing | |
MAGI'S LAB - |
RCV000671518 | SCV001426409 | pathogenic | Alstrom syndrome | 2020-08-04 | criteria provided, single submitter | clinical testing | The p.(Thr399Lysfs*11) variant has been reported in two brothers with an atypical form of Alstrom syndrome (Lombardo 2020). It is a null variant in a gene where loss-of-funcion is a known mechanism of disease. It has been found at extremely low frequency in GnomAD. The variant has been detected in trans with a pathogenic variant, the p.(Glu3771Trpfs*18). In summary, the p.(Thr399Lysfs*11) variant meets the ACMG Guidelines (Richards 2015) criteria to be classified as pathogenic (PVS1, PM2, PM3 and PP5). |
Institute of Medical Genetics and Applied Genomics, |
RCV001267997 | SCV001446562 | pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | |
Ce |
RCV001267997 | SCV001746655 | pathogenic | not provided | 2021-05-01 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000671518 | SCV002802595 | pathogenic | Alstrom syndrome | 2021-12-15 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003938021 | SCV004747773 | pathogenic | ALMS1-related condition | 2023-12-01 | criteria provided, single submitter | clinical testing | The ALMS1 c.1196_1202del7 variant is predicted to result in a frameshift and premature protein termination (p.Thr399Lysfs*11). This variant was reported in the homozygous state in brothers with Alstom syndrome (Lombardo et al. 2020. PubMed ID: 32396277). A similar deletion, c.1199_1205del, resulting in premature protein termination at the same stop codon as p.Thr399lysfs*11 has also been reported to cause Alstrom syndrome (see case 2 in Etheridge. 2020. PubMed ID: 32944671). This variant is reported in 0.0041% of alleles in individuals of European (Finnish) descent in gnomAD. Frameshift variants in ALMS1 are expected to be pathogenic. This variant is interpreted as pathogenic. |
Natera, |
RCV000671518 | SCV002080405 | pathogenic | Alstrom syndrome | 2020-11-12 | no assertion criteria provided | clinical testing |