ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.11104C>T (p.Arg3702Ter)

dbSNP: rs747747269
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001246836 SCV001420223 pathogenic Alstrom syndrome 2023-09-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg3703*) in the ALMS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ALMS1 are known to be pathogenic (PMID: 17594715). This variant is present in population databases (rs747747269, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with Alström syndrome (PMID: 24049434, 28432734). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 971131). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV002451604 SCV002739958 pathogenic Cardiovascular phenotype 2021-08-14 criteria provided, single submitter clinical testing The p.R3703* pathogenic mutation (also known as c.11107C>T), located in coding exon 16 of the ALMS1 gene, results from a C to T substitution at nucleotide position 11107. This changes the amino acid from an arginine to a stop codon within coding exon 16. This alteration, also known as p.R3701* (c.11101C>T), has been reported in numerous Alstrom syndrome cohorts, including in individuals found to be compound heterozygous for other truncation alterations in the ALMS1 gene and in one individual found to be homozygous for this alteration (Bond J et al. J Med Genet, 2005 Feb;42:e10; Minton JA et al. J Clin Endocrinol Metab, 2006 Aug;91:3110-6; Liang X et al. Mol Vis, 2013 Sep;19:1885-91; Edwards NC et al. Orphanet J Rare Dis, 2015 Jun;10:83; Zmyslowska A et al. Clin Genet, 2016 Apr;89:448-453; Baig S et al. Orphanet J Rare Dis, 2020 06;15:139). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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