ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.7288A>G (p.Ser2430Gly) (rs539112266)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000430965 SCV000532989 uncertain significance not provided 2016-10-24 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the ALMS1 gene. The S2431G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The S2431G variant was not observed in approximately 6000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The S2431G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Subsequently, although this substitution occurs at a position where amino acids with similar properties to serine are tolerated across species, G2431 is not tolerated. Splicing algorithims predict that this change may create a cryptic splice donor site that is upstream of the natural donor site, however, functional studies are necessary to determine the consequences of this change. Lastly, while some missense variants have been reported in association with Alstrom syndrome, most pathogenic variants in ALMS1 reported to date introduce a premature termination codon (Marshall et al., 2012; Stenson et al., 2014).
Invitae RCV001272961 SCV001507076 uncertain significance Alstrom syndrome 2020-09-03 criteria provided, single submitter clinical testing This sequence change replaces serine with glycine at codon 2431 of the ALMS1 protein (p.Ser2431Gly). The serine residue is weakly conserved and there is a small physicochemical difference between serine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ALMS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 390212). 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.
Natera, Inc. RCV001272961 SCV001455468 uncertain significance Alstrom syndrome 2020-03-11 no assertion criteria provided clinical testing

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