ClinVar Miner

Submissions for variant NM_024408.4(NOTCH2):c.7223T>A (p.Leu2408His)

gnomAD frequency: 0.00228  dbSNP: rs35586704
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia RCV000121737 SCV000297311 likely benign not specified 2015-12-17 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000121737 SCV000339428 likely benign not specified 2016-02-05 criteria provided, single submitter clinical testing
Invitae RCV000540032 SCV000636912 likely benign Hajdu-Cheney syndrome 2024-01-31 criteria provided, single submitter clinical testing
GeneDx RCV001711395 SCV001942685 benign not provided 2021-01-21 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Reported in possible association with primary ovarian insufficiency, congenital heart disease, and colorectal cancer (Patino et al., 2019; Patino et al., 2017; Priest et al., 2016; Timofeeva et al., 2015); Functional studies showed that p.L2408H did not demonstrate any significant change in NOTCH2 transcriptional activity compared with the wild type rates (Priest et al., 2016; Patino et al., 2019); This variant is associated with the following publications: (PMID: 28505269, 29089047, 30304577, 27058611, 26553438, 30651579, 33195954)
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV002251991 SCV002523466 likely benign See cases 2020-01-20 criteria provided, single submitter clinical testing ACMG classification criteria: BS1, BP4
Fulgent Genetics, Fulgent Genetics RCV002498576 SCV002806272 benign Alagille syndrome due to a NOTCH2 point mutation; Hajdu-Cheney syndrome 2021-10-05 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001711395 SCV004183575 benign not provided 2024-01-01 criteria provided, single submitter clinical testing NOTCH2: BS1, BS2
PreventionGenetics, part of Exact Sciences RCV003975084 SCV004799000 likely benign NOTCH2-related condition 2019-05-22 criteria provided, single submitter 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).
ITMI RCV000121737 SCV000085935 not provided not specified 2013-09-19 no assertion provided reference population
Clinical Genetics, Erasmus University Medical Center RCV000508681 SCV000328906 uncertain significance Hirschsprung disease, susceptibility to, 1 2016-11-18 no assertion criteria provided clinical testing

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