ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.9733G>A (p.Ala3245Thr)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV001175498 SCV001339096 uncertain significance not specified 2020-03-02 criteria provided, single submitter clinical testing Variant summary: ALMS1 c.9730G>A (p.Ala3244Thr) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00015 in 249478 control chromosomes, predominantly at a frequency of 0.0018 within the East Asian subpopulation in the gnomAD database. This frequency is not significantly higher than expected for a pathogenic variant in ALMS1 causing Cardiomyopathy (0.00015 vs 0.0022), allowing no conclusion about variant significance. c.9730G>A has been reported in the literature in individuals of East Asian ethnicity affected with retinitis pigmentosa without strong evidence for causality (e.g. Katagiri_2014, Xu_2015,2016). These reports do not provide unequivocal conclusions about association of the variant with Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has 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 uncertain significance.

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