ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.3729_3730del (p.Lys1244fs)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV003148289 SCV003834997 pathogenic Alstrom syndrome 2021-06-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003148289 SCV004021119 pathogenic Alstrom syndrome 2023-06-19 criteria provided, single submitter clinical testing Variant summary: ALMS1 c.3726_3727delGA/p.Lys1243AlafsX12 (also known as c.3732_3733delGA) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 248982 control chromosomes. To our knowledge, no occurrence of c.3726_3727delGA in individuals affected with Alstrom Syndrome With Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV003148289 SCV004612897 pathogenic Alstrom syndrome 2023-12-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys1245Alafs*12) 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 variant has not been reported in the literature in individuals affected with ALMS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2441969). For these reasons, this variant has been classified as Pathogenic.

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