ClinVar Miner

Submissions for variant NM_004744.5(LRAT):c.346T>C (p.Phe116Leu)

dbSNP: rs1578860322
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000987484 SCV001136783 likely pathogenic Leber congenital amaurosis 1 2019-05-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001858669 SCV002173379 uncertain significance not provided 2021-08-23 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 802098). This missense change has been observed in individuals with LRAT-related conditions (PMID: 29186038; Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with leucine at codon 116 of the LRAT protein (p.Phe116Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine.
3billion RCV002250709 SCV002521237 likely pathogenic Leber congenital amaurosis 14 2022-05-22 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.64; 3Cnet: 0.22). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with LRAT related disorder (ClinVar ID: VCV000802098 / PMID: 29186038). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 29186038, 32865313). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.

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