ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.2138_2139del (p.Ser713fs) (rs387906313)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000599323 SCV000710744 pathogenic not provided 2018-02-23 criteria provided, single submitter clinical testing The c.2141_2142delCT variant has been published in one individual with Alstrom syndrome, who harbored a second pathogenic allele in trans (Hearn et al., 2002). This variant causes a shift in reading frame starting at codon serine 714, changing it to a tyrosine, and creating a premature stop codon at position 6 of the new reading frame, denoted p.Ser714TyrfsX6. 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 frameshift variants in the ALSM1 gene have been reported in Human Gene Mutation Database in association with Alstrom syndrome, a gene for which loss-of-function is a known mechanism of disease (Stenson et al., 2014). Furthermore, the c.2141_2142delCT variant has not been observed at a significant frequency in large population cohorts (Lek et al., 2016).
Invitae RCV000004178 SCV001587016 pathogenic Alstrom syndrome 2020-08-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser714Tyrfs*6) in the ALMS1 gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in individual(s) with clinical features of Alstrom syndrome (PMID: 11941370). ClinVar contains an entry for this variant (Variation ID: 3972). Loss-of-function variants in ALMS1 are known to be pathogenic (PMID: 17594715). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000004178 SCV000024344 pathogenic Alstrom syndrome 2002-05-01 no assertion criteria provided literature only

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