ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.6668_6669insTTTTTTTTTTTTTTTTNNNNNNNNNNGGAGAGGGAGAGGGAGAGGGAGAGGGAGAGGGAGAGGGAGAGGGAGAGGGAGAGGGAGAGGGAGAGGGAGAGGGAGAGCCAAATAATGTGCTTTT (p.Leu2223delinsPhePhePhePhePhePheXaaXaaXaaXaaArgGlyArgGlyArgGlyArgGlyArgGlyArgGlyArgGlyArgGlyArgGlyArgGlyArgGlyArgGlyArgAlaLysTer)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001387592 SCV001588261 pathogenic Alstrom syndrome 2020-02-05 criteria provided, single submitter clinical testing This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 8 of the ALMS1 gene (c.6671_6672insSVA), causing a frameshift at codon 2224 (p.Leu2224fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion 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. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in ALMS1 are known to be pathogenic (PMID: 17594715). For these reasons, this variant has been classified as Pathogenic.

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