ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.6772del (p.Thr2258fs) (rs1553404310)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000523272 SCV000620074 likely pathogenic not provided 2017-08-15 criteria provided, single submitter clinical testing Although the c.6775delA likely pathogenic variant in the ALMS1 gene has not been reported to our knowledge, this variant causes a shift in reading frame starting at codon threonine 2259, changing it to a leucine, and creating a premature stop codon at position 9 of the new reading frame, denoted p.Thr2259LeufsX9. This likely pathogenic variant is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Other loss of function variants in the ALMS1 gene have been reported in Human Gene Mutation Database in association with Alstrom syndrome (Stenson et al., 2014). Furthermore, the c.6775delA variant has not been observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server).
Department of Otolaryngology – Head & Neck Surgery, Cochlear Implant Center RCV001375096 SCV001571961 likely pathogenic Stickler syndrome 2021-04-12 criteria provided, single submitter clinical testing PVS1_Strong, PM2_Moderate
Invitae RCV000984143 SCV001584866 pathogenic Alstrom syndrome 2020-10-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr2259Leufs*9) in the ALMS1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ALMS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 451381). Loss-of-function variants in ALMS1 are known to be pathogenic (PMID: 17594715). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000984143 SCV001132119 likely pathogenic Alstrom syndrome 2018-03-13 no assertion criteria provided clinical testing

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