Submissions for variant NM_001089.3(ABCA3):c.1313T>C (p.Leu438Pro)

gnomAD frequency: 0.00001  dbSNP: rs761336277

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Johns Hopkins Genomics, Johns Hopkins University	RCV001007604	SCV001167287	uncertain significance	Interstitial lung disease due to ABCA3 deficiency	2019-09-25	criteria provided, single submitter	clinical testing	This ABCA3 variant (rs761336277) is rare (<0.1%) in a large population datasets (gnomAD: 1/250838 total alleles; 0.0003987%; no homozygotes), and has not been reported in the literature, to our knowledge. Of three bioinformatics tools queried, two predict that the substitution would be possibly damaging, while the third predicts that it would be tolerated. Additionally, the leucine residue at this position is evolutionarily conserved only among higher order species. The clinical significance of c.1313T>C is uncertain at this time.
Ambry Genetics	RCV002382244	SCV002691678	uncertain significance	Hereditary pulmonary alveolar proteinosis	2019-01-30	criteria provided, single submitter	clinical testing	The p.L438P variant (also known as c.1313T>C), located in coding exon 9 of the ABCA3 gene, results from a T to C substitution at nucleotide position 1313. The leucine at codon 438 is replaced by proline, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.