ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.4228G>C (p.Ala1410Pro)

gnomAD frequency: 0.00022  dbSNP: rs201517720
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000634777 SCV000756120 uncertain significance Alstrom syndrome 2022-10-13 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1411 of the ALMS1 protein (p.Ala1411Pro). This variant is present in population databases (rs201517720, 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: 529369). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Not Available"; Align-GVGD: "Not Available". The proline amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
GeneDx RCV001702699 SCV002038960 uncertain significance not provided 2023-03-29 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
Genetic Services Laboratory, University of Chicago RCV001701140 SCV002070954 uncertain significance not specified 2019-01-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV002331133 SCV002630446 uncertain significance Cardiovascular phenotype 2023-05-11 criteria provided, single submitter clinical testing The p.A1411P variant (also known as c.4231G>C), located in coding exon 8 of the ALMS1 gene, results from a G to C substitution at nucleotide position 4231. The alanine at codon 1411 is replaced by proline, an amino acid with highly similar properties. This amino acid position is not well 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 RCV000634777 SCV002780990 uncertain significance Alstrom syndrome 2022-02-18 criteria provided, single submitter clinical testing
Natera, Inc. RCV000634777 SCV001463042 uncertain significance Alstrom syndrome 2020-09-16 no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV001701140 SCV001921422 benign not specified no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV001702699 SCV001927377 likely benign not provided no assertion criteria provided clinical testing

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