Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000705168 | SCV000834153 | uncertain significance | Alstrom syndrome | 2022-11-02 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 3986 of the ALMS1 protein (p.Ile3986Val). This variant is present in population databases (rs201728850, gnomAD 0.2%). 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: 581362). 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 valine 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. |
Fulgent Genetics, |
RCV000705168 | SCV000897049 | uncertain significance | Alstrom syndrome | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV001195324 | SCV001365667 | likely benign | not specified | 2019-10-04 | criteria provided, single submitter | clinical testing | The p.Ile3986Val variant in ALMS1 is classified as likely benign because it has been identified in 0.1% (59/35436) of Latino chromosomes by gnomAD (http://gnomad.broadinstitute.org), and computational prediction tools predict that this variant does not impact the protein. ACMG/AMP Criteria applied: BS1_Supporting, BP4. |
Genome- |
RCV000705168 | SCV001652731 | likely benign | Alstrom syndrome | 2021-05-18 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001560085 | SCV001782424 | uncertain significance | not provided | 2023-10-17 | 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, |
RCV001195324 | SCV002066449 | uncertain significance | not specified | 2019-05-01 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002334381 | SCV002641112 | likely benign | Cardiovascular phenotype | 2019-10-14 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
New York Genome Center | RCV000705168 | SCV003925100 | uncertain significance | Alstrom syndrome | 2021-12-09 | criteria provided, single submitter | clinical testing | The heterozygous c.11953A>G (p.Ile3986Val) missense variant identified in the ALMS1 gene has not been reported in affected individuals in the literature. The variant has 0.0003620 allele frequency in the gnomAD (v2.1.1 and v3.1.2) database (102 out of 281762 heterozygous alleles, no homozygotes). This variant is reported as both a Variant of uncertain significance and likely benign associated with Alstrom syndrome in the ClinVar database (Variation ID: 581362). The variant affects a weakly conserved residue (Ile3986) of ALMS1 protein and is predicted neutral by multiple in silico prediction tools (CADD score = 6.015, REVEL score= 0.243). Based on the available evidence, the heterozygous c.11953A>G (p.Ile3986Val) missense variant identified in the ALMS1 gene is reported as a Variant of Uncertain Significance. |
Natera, |
RCV000705168 | SCV001459608 | likely benign | Alstrom syndrome | 2020-04-23 | no assertion criteria provided | clinical testing |