ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.1867T>C (p.Ser623Pro)

gnomAD frequency: 0.00010  dbSNP: rs767987501
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000192980 SCV000246356 uncertain significance not specified 2015-07-02 criteria provided, single submitter clinical testing
GeneDx RCV000767036 SCV000492097 uncertain significance not provided 2023-08-10 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
Invitae RCV000801509 SCV000941286 uncertain significance Alstrom syndrome 2022-10-12 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 624 of the ALMS1 protein (p.Ser624Pro). This variant is present in population databases (rs767987501, 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: 210125). 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.
Ambry Genetics RCV002408854 SCV002723201 uncertain significance Cardiovascular phenotype 2022-06-30 criteria provided, single submitter clinical testing The p.S624P variant (also known as c.1870T>C), located in coding exon 8 of the ALMS1 gene, results from a T to C substitution at nucleotide position 1870. The serine at codon 624 is replaced by proline, an amino acid with 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.
Natera, Inc. RCV000801509 SCV001458906 uncertain significance Alstrom syndrome 2020-09-16 no assertion criteria provided clinical testing

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