Submissions for variant NM_000075.4(CDK4):c.222G>A (p.Leu74=)

gnomAD frequency: 0.00001  dbSNP: rs565645344

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000564786	SCV000669111	likely benign	Hereditary cancer-predisposing syndrome	2017-03-15	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	RCV000869772	SCV001011227	likely benign	Familial melanoma	2024-10-12	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001290614	SCV001478715	likely benign	not specified	2021-01-15	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV003478256	SCV004220851	likely benign	not provided	2022-10-07	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV004787939	SCV005404183	benign	Melanoma, cutaneous malignant, susceptibility to, 3	2024-09-25	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.
PreventionGenetics, part of Exact Sciences	RCV003980053	SCV004795548	likely benign	CDK4-related disorder	2023-12-14	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).