Submissions for variant NM_016103.4(SAR1B):c.83_84del (p.Leu28fs)

gnomAD frequency: 0.00003  dbSNP: rs755928019

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002568511	SCV003737910	pathogenic	Inborn genetic diseases	2022-07-17	criteria provided, single submitter	clinical testing	The c.83_84delTG (p.L28Rfs*7) alteration, located in exon 4 (coding exon 2) of the SAR1B gene, consists of a deletion of 2 nucleotides from position 83 to 84, causing a translational frameshift with a predicted alternate stop codon after 7 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from gnomAD, the c.83_84delTG allele has an overall frequency of <0.01% (6/251398) total alleles studied. The highest observed frequency was 0.01% (6/113708) of European (non-Finnish) alleles. This variant was identified in the homozygous state in several individuals with chylomicron retention disease (Georges, 2011; Ferreira, 2018; Blanco-Vaca, 2019). In one family, the affected proband was homozygous for this variant as was the proband's mother who had no evidence of chylomicron retention disease (Cefal&ugrave;, 2010). Based on the available evidence, this alteration is classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001579414	SCV004548877	pathogenic	not provided	2023-08-14	criteria provided, single submitter	clinical testing	This variant is present in population databases (rs755928019, gnomAD 0.005%). This premature translational stop signal has been observed in individual(s) with clinical features of chylomicron retention disease (PMID: 21235735, 29713611, 30782561). ClinVar contains an entry for this variant (Variation ID: 1209895). For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Leu28Argfs*7) in the SAR1B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SAR1B are known to be pathogenic (PMID: 12692552, 17945526).
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001579414	SCV001807146	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001579414	SCV001923318	pathogenic	not provided		no assertion criteria provided	clinical testing