ClinVar Miner

Submissions for variant NM_016103.4(SAR1B):c.409G>A (p.Asp137Asn)

gnomAD frequency: 0.00004  dbSNP: rs28942109
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000725750 SCV000339143 pathogenic not provided 2018-03-22 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000003057 SCV000731534 likely pathogenic Chylomicron retention disease 2017-07-28 criteria provided, single submitter clinical testing The p.Asp137Asn (NM_001033503.2 c.409G>A) variant in SAR1B has been reported in at least 5 homozygous and 3 compound heterozygous individuals of French Canadian or White Canadian ancestry with Chylomicron retention disease and segregated in 5 family members (Charcosset 2008, Peretti 2009, and Jones 2003). This variant has also been reported in ClinVar (Variation ID#2923). This variant has been ide ntified in 0.004% (2/53,150) of European chromosomes by the Exome Aggregation Co nsortium (ExAC, http://exac.broadinstitute.org; dbSNP rs28942109). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. Computational prediction tool s and conservation analysis suggest that the p.Asp137Asn variant may impact the protein, though this information is not predictive enough to determine pathogeni city. In summary, although additional studies are required to fully establish it s clinical significance, the p.Asp137Asn variant is likely pathogenic based upon biallelic case observations and segregation in affected individuals.
Revvity Omics, Revvity RCV000003057 SCV002019120 likely pathogenic Chylomicron retention disease 2020-02-19 criteria provided, single submitter clinical testing
Invitae RCV000725750 SCV004292853 pathogenic not provided 2023-07-07 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 2923). This missense change has been observed in individuals with Anderson's disease and/or chylomicron retention disease (PMID: 12692552, 17945526). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs28942109, gnomAD 0.005%). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 137 of the SAR1B protein (p.Asp137Asn).
OMIM RCV000003057 SCV000023215 pathogenic Chylomicron retention disease 2008-01-01 no assertion criteria provided literature only
GeneReviews RCV000003057 SCV002318918 not provided Chylomicron retention disease no assertion provided literature only

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