Submissions for variant NM_002528.7(NTHL1):c.74G>A (p.Arg25Lys)

gnomAD frequency: 0.00029  dbSNP: rs2302172

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000879706	SCV001022754	likely benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001019876	SCV001181288	likely benign	Hereditary cancer-predisposing syndrome	2018-05-09	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.
GeneDx	RCV000879706	SCV001804206	uncertain significance	not provided	2024-05-01	criteria provided, single submitter	clinical testing	Published functional studies demonstrate this variant induces cellular transformation but does not impact cellular localization or enzymatic functions of NTHL1 (PMID: 32595826); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in individuals with breast cancer (PMID: 33980861); This variant is associated with the following publications: (PMID: 33087284, 26400813, 21167187, 34363023, 32595826, 33980861)
CeGaT Center for Human Genetics Tuebingen	RCV000879706	SCV002497852	benign	not provided	2022-05-01	criteria provided, single submitter	clinical testing	TSC2: BS1, BS2
Sema4, Sema4	RCV001019876	SCV002529035	likely benign	Hereditary cancer-predisposing syndrome	2021-05-25	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV003321759	SCV004027053	uncertain significance	not specified	2024-07-31	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003955796	SCV004777358	likely benign	NTHL1-related disorder	2021-04-20	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).