ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.4888C>T (p.Gln1630Ter)

gnomAD frequency: 0.00001  dbSNP: rs974309886
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001733459 SCV001983865 pathogenic not provided 2021-10-26 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 in large population cohorts (Lek et al., 2016); Previously reported in two individuals with Alstrom syndrome in published literature, although additional phenotypic and segregation information was not provided (Marshall et al., 2015); This variant is associated with the following publications: (PMID: 26992781, 25846608, 26010121)
Labcorp Genetics (formerly Invitae), Labcorp RCV002032733 SCV002234138 pathogenic Alstrom syndrome 2023-12-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1631*) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Alstrom syndrome (PMID: 25846608, 26992781). ClinVar contains an entry for this variant (Variation ID: 1301455). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV003365442 SCV004056895 pathogenic Cardiovascular phenotype 2023-07-10 criteria provided, single submitter clinical testing The p.Q1631* pathogenic mutation (also known as c.4891C>T), located in coding exon 8 of the ALMS1 gene, results from a C to T substitution at nucleotide position 4891. This changes the amino acid from a glutamine to a stop codon within coding exon 8. This alteration has been reported in Alstrom syndrome and cone rod dystrophy cohorts (Marshall JD et al. Hum Mutat, 2015 Jul;36:660-8; Huang L et al. Exp Eye Res, 2016 May;146:252-258). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.

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