ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.2059C>T (p.His687Tyr)

gnomAD frequency: 0.00002  dbSNP: rs771266951
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV001449788 SCV001653066 likely benign not specified 2020-09-16 criteria provided, single submitter clinical testing The His686Tyr (also known as p.His688Tyr) variant in ALMS1 is classified as likely benign due to a lack of conservation across species. Five mammals (Chinese hamster, guinea pig, Bactrian camel, cat, and cape golden mole) carry a tyrosine at this position. In addition, computational prediction tools predict that this variant does not impact the protein. It has not been previously reported in individuals with hearing loss or Alstrom Syndrome but has been identified in 0.002% (2/112716) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). ACMG/AMP criteria applied: PM2, BP4_Strong, BP4.
Labcorp Genetics (formerly Invitae), Labcorp RCV001872006 SCV002153724 uncertain significance Alstrom syndrome 2022-04-07 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 688 of the ALMS1 protein (p.His688Tyr). This variant is present in population databases (rs771266951, gnomAD 0.002%). 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: 1120112). 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.
Ambry Genetics RCV004038480 SCV005026830 likely benign Cardiovascular phenotype 2023-10-25 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
GeneDx RCV004779121 SCV005391067 uncertain significance not provided 2024-04-09 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge; In silico analysis does not support a benign or deleterious effect of this variant on protein structure/function

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