ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.6143A>G (p.Tyr2048Cys)

gnomAD frequency: 0.00005  dbSNP: rs201162418
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000667685 SCV000792173 uncertain significance Alstrom syndrome 2017-06-16 criteria provided, single submitter clinical testing
Ambry Genetics RCV002352091 SCV002654919 uncertain significance Cardiovascular phenotype 2023-06-23 criteria provided, single submitter clinical testing The p.Y2049C variant (also known as c.6146A>G), located in coding exon 8 of the ALMS1 gene, results from an A to G substitution at nucleotide position 6146. The tyrosine at codon 2049 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is well conserved in available vertebrate species; however, cysteine is the reference amino acid in other 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 RCV000667685 SCV002816176 uncertain significance Alstrom syndrome 2022-01-04 criteria provided, single submitter clinical testing
Invitae RCV000667685 SCV003245273 uncertain significance Alstrom syndrome 2022-05-04 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 2049 of the ALMS1 protein (p.Tyr2049Cys). This variant is present in population databases (rs201162418, 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: 552428). 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 cysteine 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.

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