Submissions for variant NM_001378454.1(ALMS1):c.861C>T (p.Asp287=)

gnomAD frequency: 0.00028  dbSNP: rs377281121

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000634818	SCV000756162	likely benign	Alstrom syndrome	2024-01-29	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000735884	SCV000864104	uncertain significance	not specified	2018-03-12	criteria provided, single submitter	clinical testing	Variant summary: ALMS1 c.861C>T (alternative c.864C>T) alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant is found in the gnomAD database at a frequency of 0.00014. This frequency is not higher than expected for a pathogenic variant in ALMS1 causing Cardiomyopathy (0.00014 vs 0.0022), allowing no conclusion about variant significance. The c.861C>T variant has been reported in the literature in one individual affected with Alstrom syndrome. This report does not provide unequivocal conclusions about an association of the variant with Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
GeneDx	RCV001571784	SCV001796317	likely benign	not provided	2021-01-13	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002377375	SCV002684250	likely benign	Cardiovascular phenotype	2020-05-29	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.
Clinical Genetics, Academic Medical Center	RCV000735884	SCV001918496	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001571784	SCV001970861	likely benign	not provided		no assertion criteria provided	clinical testing