ClinVar Miner

Submissions for variant NM_015120.4(ALMS1):c.5465C>T (p.Pro1822Leu) (rs200266868)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000227137 SCV000290093 uncertain significance Alstrom syndrome 2018-10-23 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 1822 of the ALMS1 protein (p.Pro1822Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs200266868, ExAC 0.09%). This variant has been reported in the heterozygous state in an individual affected with Alstrom syndrome who did not have a second variant identified (PMID: 22876109). ClinVar contains an entry for this variant (Variation ID: 241003). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably damaging"; Align-GVGD: "Class C0"). In summary, this is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
GeneDx RCV000731515 SCV000619195 uncertain significance not provided 2017-07-14 criteria provided, single submitter clinical testing A second variant of uncertain significance has been identified in the ALMS1 gene. The P1822L variant has been published as a heterozygous variant in one patient with Alstrom syndrome (Pineiro-Gallego et al., 2012). The P1822L variant is observed in 9/9708 (0.1%) alleles from individuals of African ancestry in the Exome Aggregation Consortium (Lek et al., 2016; Exome Variant Server). This substitution occurs at a position that is not conserved across species and where leucine (L) is present as the wild type in at least one species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Nevertheless, the P1822L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties.
Counsyl RCV000227137 SCV000790173 uncertain significance Alstrom syndrome 2017-03-07 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000731515 SCV000859344 uncertain significance not provided 2018-02-02 criteria provided, single submitter clinical testing

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