ClinVar Miner

Submissions for variant NM_001089.3(ABCA3):c.2309C>T (p.Pro770Leu) (rs143929832)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000345051 SCV000395994 uncertain significance Surfactant metabolism dysfunction, pulmonary, 3 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx RCV000732937 SCV000520874 uncertain significance not provided 2018-03-13 criteria provided, single submitter clinical testing The P770L variant in the ABCA3 gene has been previously reported as a single heterozygous variant in an infant with interstitial lung disease; a second variant in ABCA3, as would be expected with autosomal recessive ABCA3-related lung disease, was not identified and further evidence supporting the pathogenicity of this variant was not specified (Griese et al., 2015). Although not present in the homozygous state, the NHLBI ESP Exome Sequencing Project reports P770L was observed in 16/8600 (0.19%) alleles from individuals of European American background, indicating it may be a rare variant in this population. The P770L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret P770L as a variant of uncertain significance.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000732937 SCV000860938 uncertain significance not provided 2018-05-18 criteria provided, single submitter clinical testing
Invitae RCV000732937 SCV001048963 likely benign not provided 2019-12-31 criteria provided, single submitter clinical testing
Johns Hopkins Genomics, Johns Hopkins University RCV000345051 SCV001478416 uncertain significance Surfactant metabolism dysfunction, pulmonary, 3 2021-01-29 criteria provided, single submitter clinical testing

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