Submissions for variant NM_194454.3(KRIT1):c.1384A>G (p.Thr462Ala)

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002381230	SCV002696491	likely benign	Inborn genetic diseases	2023-02-09	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003633653	SCV004465705	likely benign	Cerebral cavernous malformation	2023-08-21	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004801210	SCV005422764	uncertain significance	not specified	2024-10-17	criteria provided, single submitter	clinical testing	Variant summary: KRIT1 c.1384A>G (p.Thr462Ala) results in a non-conservative amino acid change located in the FERM domain of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 5.6e-05 in 251152 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in KRIT1 causing KRIT1-Related Disorders, allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1384A>G in individuals affected with KRIT1-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1771352). Based on the evidence outlined above, the variant was classified as uncertain significance.
PreventionGenetics, part of Exact Sciences	RCV004548289	SCV004780241	likely benign	KRIT1-related disorder	2021-08-11	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).