ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.3412A>G (p.Thr1138Ala)

gnomAD frequency: 0.00002  dbSNP: rs201884768
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000634786 SCV000756129 uncertain significance Alstrom syndrome 2022-08-08 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 1139 of the ALMS1 protein (p.Thr1139Ala). This variant is present in population databases (rs201884768, gnomAD 0.01%). 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: 529375). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Counsyl RCV000634786 SCV000791251 uncertain significance Alstrom syndrome 2017-05-15 criteria provided, single submitter clinical testing
GeneDx RCV002264966 SCV002546662 uncertain significance not provided 2022-07-06 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002458020 SCV002616532 uncertain significance Cardiovascular phenotype 2022-09-06 criteria provided, single submitter clinical testing The p.T1139A variant (also known as c.3415A>G), located in coding exon 8 of the ALMS1 gene, results from an A to G substitution at nucleotide position 3415. The threonine at codon 1139 is replaced by alanine, an amino acid with similar properties. This variant was detected in the heterozygous state in one of two siblings with non-syndromic hearing loss in whom additional variants in other hearing loss-related genes were also detected (Khalil A et al. BMC Med Genet. 2020 01;21(1):1). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV000634786 SCV002791293 uncertain significance Alstrom syndrome 2021-11-22 criteria provided, single submitter clinical testing
Natera, Inc. RCV000634786 SCV001453450 uncertain significance Alstrom syndrome 2020-03-17 no assertion criteria provided clinical testing

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