Submissions for variant NM_001378454.1(ALMS1):c.833_834del (p.Phe278fs)

Minimum review status:		Collection method:
Minimum conflict level: Report conflict between different conditions
		ClinVar version:

Total submissions: 3

Download table as spreadsheet

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001724806	SCV001950205	likely pathogenic	Retinitis pigmentosa	2021-04-01	criteria provided, single submitter	curation	The p.Phe278SerfsTer16 variant in ALMS1 was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Pierce lab (https://oculargenomics.meei.harvard.edu/labs/pierce-lab/lab-members/). Through a review of available evidence we were able to apply the following criteria: PVS1, PM2. Based on this evidence we have classified this variant as Likely Pathogenic. If you have any questions about the classification please reach out to the Pierce Lab.
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV002227532	SCV002507019	pathogenic	Alstrom syndrome	2022-05-04	criteria provided, single submitter	curation	The heterozygous p.Phe278SerfsTer16 variant in ALMS1 was identified by our study in the compound heterozygous state, along with another pathogenic variant, in 1 individual with Alstrom syndrome. The variant has not been previously reported in individuals with Alstrom syndrome and was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 278 and leads to a premature termination codon 16 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the ALMS1 gene is an established disease mechanism in autosomal recessive Alstrom syndrome. The presence of this variant in combination with a reported pathogenic variants increases the likelihood that the p.Phe278SerfsTer16 variant is pathogenic (Variation ID: 550627). In summary, this variant meets criteria to be classified as pathogenic for Alstrom syndrome in an autosomal recessive manner based on the predicted impact of the variant, its absence from control populations, and its occurrence in trans with another pathogenic variant. ACMG/AMP Criteria applied: PVS1, PM2, PM3 (Richards 2015).
Labcorp Genetics (formerly Invitae), Labcorp	RCV002227532	SCV004551130	pathogenic	Alstrom syndrome	2023-06-17	criteria provided, single submitter	clinical testing	This premature translational stop signal has been observed in individual(s) with inherited retinal dystrophy (PMID: 32037395). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Phe279Serfs*16) 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 also known as c.833_834delTC. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1297102).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.