Submissions for variant NM_001378454.1(ALMS1):c.3718_3721del (p.Ser1240fs)

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Total submissions: 3

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001251283	SCV001426815	likely pathogenic	Alstrom syndrome	2020-07-22	criteria provided, single submitter	clinical testing	Variant summary: ALMS1 c.3715_3718delTCAC (p.Ser1239ThrfsX23) 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. Truncations downstream of this position have been classified as pathogenic (in ClinVar and in HGMD). The variant was absent in 249040 control chromosomes (gnomAD). To our knowledge, no occurrence of c.3715_3718delTCAC in individuals affected with Alstrom Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV001251283	SCV002802431	likely pathogenic	Alstrom syndrome	2021-11-05	criteria provided, single submitter	clinical testing
Invitae	RCV001251283	SCV004675210	pathogenic	Alstrom syndrome	2024-01-19	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ser1241Thrfs*23) 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: 974960). For these reasons, this variant has been classified as Pathogenic.

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