ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.1658_1659del (p.Lys553fs)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV001449737 SCV001653008 likely pathogenic Alstrom syndrome 2020-06-09 criteria provided, single submitter clinical testing The c.1661_1662delAA, p.Lys554SerfsX6 variant in ALMS1 has not been previously reported in individuals with Alstrom syndrome and was absent from large population studies. Please note that due to a discrepancy between the NM_015120.4 transcript and the GRCh37/hg19 genomic sequence in which NM_015120.4 transcript has 2 extra codons and 6 extra nucleotides. Therefore, this variant may also be referred to as c.1655_1656delAA, p.Lys552SerfsX6. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 554 and leads to a premature termination codon 6 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the ALMS1 gene is an established disease mechanism in autosomal recessive Alstrom syndrome. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive Alstrom syndrome. ACMG/AMP Criteria applied: PVS1, PM2.

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