Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000668239 | SCV000792811 | pathogenic | Alpha-1-antitrypsin deficiency | 2017-07-17 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000668239 | SCV001591487 | pathogenic | Alpha-1-antitrypsin deficiency | 2020-05-21 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the SERPINA1 protein. Other variant(s) that disrupt this region (p.Glu387Argfs*14) have been determined to be pathogenic (PMID: 9070606, 11334395, 22016686). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has been reported to affect SERPINA1 protein function (PMID: 2539391). This variant has been observed in individual(s) with alpha-1-antitrypsin deficiency (PMID: 2539391, 21457231). It has also been observed to segregate with disease in related individuals. This variant is also known as Null Mattawa, L353fsX376, c.1126->T and Q0nancy in the literature. ClinVar contains an entry for this variant (Variation ID: 552891). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change results in a premature translational stop signal in the SERPINA1 gene (p.Leu377Phefs*24). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 42 amino acids of the SERPINA1 protein. |
Baylor Genetics | RCV000668239 | SCV004203121 | pathogenic | Alpha-1-antitrypsin deficiency | 2023-09-12 | criteria provided, single submitter | clinical testing | |
Child Health and Human Development Program, |
RCV000668239 | SCV001424552 | pathogenic | Alpha-1-antitrypsin deficiency | no assertion criteria provided | clinical testing | The homozygous duplication of a single nucleotide [c.1130dup (p.Leu377fs)] in SERPINA1 was identified in a 65 year old female of Latin American origin being treated for emphysema. Her AAT level was 0.10 g/L. The AAT reference range at our institution is 0.99-2.59 g/L. |