Submissions for variant NM_000477.7(ALB):c.412C>T (p.Arg138Ter)

gnomAD frequency: 0.00002  dbSNP: rs77238412

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000144404	SCV000711778	pathogenic	Analbuminemia	2016-03-02	criteria provided, single submitter	clinical testing	The p.Arg138X variant in ALB has been reported in 2 homozygous individuals with congenital analbuminemia Watkins 1994, Campagnoli 2005). This variant has also b een identified in 1/66370 of European chromosomes by the Exome Aggregation Conso rtium (ExAC, http://exac.broadinstitute.org; dbSNP rs77238412). Although this v ariant has been seen in the general population, its frequency is low enough to b e consistent with a recessive carrier frequency. This nonsense variant leads to a premature termination codon at position 138, which is predicted to lead to a t runcated or absent protein. In summary, this variant meets our criteria to be cl assified as pathogenic for congenital analbuminemia in an autosomal recessive ma nner based upon reports in affected individuals and predicted functional impact on the protein.
GeneDx	RCV003441754	SCV004168898	pathogenic	not provided	2023-09-30	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34662886, 25525159, 7937781, 20415703, 15996651, 15300429, 30609409, 32181025, 32553838)
ClinVar Staff, National Center for Biotechnology Information (NCBI)	RCV000144404	SCV000189459	not provided	Analbuminemia		no assertion provided	not provided
OMIM	RCV000144404	SCV001683260	pathogenic	Analbuminemia	1994-03-15	no assertion criteria provided	literature only