ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.2819T>A (p.Leu940Ter)

gnomAD frequency: 0.00001  dbSNP: rs539612316
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Diagnostics Division, CENTRE FOR DNA FINGERPRINTING AND DIAGNOSTICS RCV000210366 SCV000259178 pathogenic Alstrom syndrome 2015-12-01 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV000210366 SCV000756143 pathogenic Alstrom syndrome 2024-01-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu941*) 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 (rs539612316, gnomAD 0.006%). This premature translational stop signal has been observed in individuals with Alstrom syndrome (PMID: 26111748, 27665122). ClinVar contains an entry for this variant (Variation ID: 224801). For these reasons, this variant has been classified as Pathogenic.
Genetic Services Laboratory, University of Chicago RCV001818509 SCV002069210 pathogenic not provided 2018-12-09 criteria provided, single submitter clinical testing
Laboratory of Medical Genetics (UMR_S 1112), INSERM/Strasbourg University RCV000210366 SCV002559828 pathogenic Alstrom syndrome 2022-08-09 criteria provided, single submitter clinical testing
Ambry Genetics RCV002433919 SCV002746667 pathogenic Cardiovascular phenotype 2021-01-06 criteria provided, single submitter clinical testing The p.L941* pathogenic mutation (also known as c.2822T>A), located in coding exon 8 of the ALMS1 gene, results from a T to A substitution at nucleotide position 2822. This changes the amino acid from a leucine to a stop codon within coding exon 8. This mutation (also referred to as c.2816T>A, p.L939*) has been detected in the homozygous state and in the compound heterozygous state with ALMS1 nonsense and frameshift alleles in individuals with Alstrom syndrome (Marshall JD et al. Hum Mutat, 2015 Jul;36:660-8; Das Bhowmik A et al. Obes Res Clin Pract , 2017 Sep;11:241-246; Baig S et al. Orphanet J Rare Dis, 2020 06;15:139). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Fulgent Genetics, Fulgent Genetics RCV000210366 SCV002808687 pathogenic Alstrom syndrome 2022-04-06 criteria provided, single submitter clinical testing
GeneDx RCV001818509 SCV005327058 pathogenic not provided 2023-12-15 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25846608, 26111748, 32503575, 27665122, 35211159)
Natera, Inc. RCV000210366 SCV001458918 pathogenic Alstrom syndrome 2020-09-16 no assertion criteria provided clinical testing

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