ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.1196_1202del (p.Thr399fs)

dbSNP: rs761292021
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Total submissions: 9
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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 - Medical Genetics Laboratory, MAGI GROUP 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, University Hospital Tübingen RCV001267997 SCV001446562 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001267997 SCV001746655 pathogenic not provided 2021-05-01 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000671518 SCV002802595 pathogenic Alstrom syndrome 2021-12-15 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences 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, Inc. RCV000671518 SCV002080405 pathogenic Alstrom syndrome 2020-11-12 no assertion criteria provided clinical testing

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