ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.1886G>A (p.Gly629Asp)

gnomAD frequency: 0.00004  dbSNP: rs531859344
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000697141 SCV000825737 uncertain significance Alstrom syndrome 2022-10-17 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 630 of the ALMS1 protein (p.Gly630Asp). This variant is present in population databases (rs531859344, gnomAD 0.02%). 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: 575048). 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.
Johns Hopkins Genomics, Johns Hopkins University RCV000697141 SCV001548515 uncertain significance Alstrom syndrome 2021-03-22 criteria provided, single submitter clinical testing ALMS1 c.1883G>A (rs531859344) is rare (<0.1%) in a large population dataset (gnomAD: 5/280468 total alleles; 0.0018%; no homozygotes). This ALMS1 variant has not been reported in the literature to our knowledge, but there is an entry for this variant in ClinVar (Variation ID: 575048). Of three bioinformatics tools queried, one predicts that the substitution would be possibly damaging, while two predict that it would be tolerated. The glycine residue at this position is not highly evolutionarily conserved among the species assessed. Due to insufficient evidence, we consider the clinical significance of c.1883G>A to be uncertain at this time.
Ambry Genetics RCV002406602 SCV002717389 uncertain significance Cardiovascular phenotype 2022-10-06 criteria provided, single submitter clinical testing The p.G630D variant (also known as c.1889G>A), located in coding exon 8 of the ALMS1 gene, results from a G to A substitution at nucleotide position 1889. The glycine at codon 630 is replaced by aspartic acid, an amino acid with similar properties. 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 RCV000697141 SCV002794081 uncertain significance Alstrom syndrome 2021-12-23 criteria provided, single submitter clinical testing
GeneDx RCV003442039 SCV004167996 uncertain significance not provided 2023-04-26 criteria provided, single submitter clinical testing 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
Natera, Inc. RCV000697141 SCV002080435 uncertain significance Alstrom syndrome 2021-10-06 no assertion criteria provided clinical testing

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