Submissions for variant NM_020738.4(KIDINS220):c.3374dup (p.Tyr1125Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV003419215	SCV004116904	likely pathogenic	KIDINS220-related disorder	2022-09-27	criteria provided, single submitter	clinical testing	The KIDINS220 c.3374dupA variant is predicted to result in premature protein termination (p.Tyr1125*). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-8890281-G-GT). Nonsense variants in KIDINS220 are expected to be pathogenic. However, this variant is located in exon 24 of 30, and therefore is expected to be pathogenic only for autosomal recessive KIDINS220 associated disorders. This variant is interpreted as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV005099966	SCV005779093	pathogenic	not provided	2025-01-05	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Tyr1125*) in the KIDINS220 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KIDINS220 are known to be pathogenic (PMID: 28934391, 32909676). This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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: 2635940). For these reasons, this variant has been classified as Pathogenic.