Submissions for variant NM_020738.4(KIDINS220):c.4658C>T (p.Pro1553Leu)

gnomAD frequency: 0.00001  dbSNP: rs76169344

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002034302	SCV002307515	uncertain significance	not provided	2024-04-29	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1553 of the KIDINS220 protein (p.Pro1553Leu). This variant is present in population databases (rs76169344, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with KIDINS220-related conditions. ClinVar contains an entry for this variant (Variation ID: 1522195). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
PreventionGenetics, part of Exact Sciences	RCV003408100	SCV004115998	uncertain significance	KIDINS220-related disorder	2024-06-06	no assertion criteria provided	clinical testing	The KIDINS220 c.4658C>T variant is predicted to result in the amino acid substitution p.Pro1553Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.016% of alleles in individuals of South Asian descent in gnomAD, which may be too common to be an undocumented primary cause of an autosomal dominant disease. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.