Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000665643 | SCV000789796 | pathogenic | Alstrom syndrome | 2017-03-16 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000665643 | SCV000832686 | pathogenic | Alstrom syndrome | 2023-12-21 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu3773Trpfs*18) 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 (rs747272625, gnomAD 0.005%). This premature translational stop signal has been observed in individuals with Alstrom syndrome (PMID: 17594715). ClinVar contains an entry for this variant (Variation ID: 550797). For these reasons, this variant has been classified as Pathogenic. |
MAGI'S LAB - |
RCV000665643 | SCV001426410 | pathogenic | Alstrom syndrome | 2020-08-04 | criteria provided, single submitter | clinical testing | The p.(Glu3771Trpfs*18) variant has been reported in association with Alstrom syndrome (Marshall 2015). 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.(Thr399Lysfs*11). In summary, the p.(Glu3771Trpfs*18) variant meets the ACMG Guidelines (Richards 2015) criteria to be classified as pathogenic (PVS1, PM2, PM3 and PP5). |
Fulgent Genetics, |
RCV000665643 | SCV002816872 | pathogenic | Alstrom syndrome | 2021-08-05 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002530660 | SCV003550063 | pathogenic | Inborn genetic diseases | 2022-03-15 | criteria provided, single submitter | clinical testing | The c.11316_11319delAGAG (p.E3773Wfs*18) alteration, located in exon 16 (coding exon 16) of the ALMS1 gene, consists of a deletion of 4 nucleotides from position 11316 to 11319, causing a translational frameshift with a predicted alternate stop codon after 18 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from gnomAD, this alteration has an overall frequency of <0.01% (6/247766) total alleles studied. The highest observed frequency was 0.01% (6/112268) of European (non-Finnish) alleles. This alteration has been reported homozygous or compound heterozygous in multiple unrelated patients with Alstrom syndrome (Marshall, 2007). Based on the available evidence, this alteration is classified as pathogenic. |
Natera, |
RCV000665643 | SCV002079005 | pathogenic | Alstrom syndrome | 2020-08-27 | no assertion criteria provided | clinical testing |