Submissions for variant NM_024513.4(FYCO1):c.425T>C (p.Leu142Pro)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002966404	SCV003278319	uncertain significance	Cataract 18	2023-06-16	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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 2067347). This missense change has been observed in individual(s) with congenital cataracts (Invitae). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs763972976, gnomAD 0.01%). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 142 of the FYCO1 protein (p.Leu142Pro).
PreventionGenetics, part of Exact Sciences	RCV003418669	SCV004117045	uncertain significance	FYCO1-related disorder	2024-08-30	no assertion criteria provided	clinical testing	The FYCO1 c.425T>C variant is predicted to result in the amino acid substitution p.Leu142Pro. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.012% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.