NM_002382.5(MAX):c.25G>T (p.Val9Leu) AND Hereditary cancer-predisposing syndrome

Clinical significance:Uncertain significance (Last evaluated: Feb 27, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000569331.2

Allele description [Variation Report for NM_002382.5(MAX):c.25G>T (p.Val9Leu)]

NM_002382.5(MAX):c.25G>T (p.Val9Leu)

Gene:
MAX:MYC associated factor X [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
14q23.3
Genomic location:
Preferred name:
NM_002382.5(MAX):c.25G>T (p.Val9Leu)
HGVS:
  • NC_000014.9:g.65102315C>A
  • NG_029830.1:g.5195G>T
  • NM_001271068.2:c.25G>T
  • NM_001271069.2:c.25G>T
  • NM_001320415.2:c.-250G>T
  • NM_002382.5:c.25G>TMANE SELECT
  • NM_145112.3:c.25G>T
  • NM_145113.3:c.25G>T
  • NM_145114.3:c.25G>T
  • NM_197957.4:c.25G>T
  • NP_001257997.1:p.Val9Leu
  • NP_001257998.1:p.Val9Leu
  • NP_002373.3:p.Val9Leu
  • NP_660087.1:p.Val9Leu
  • NP_660088.1:p.Val9Leu
  • NP_660089.1:p.Val9Leu
  • NP_932061.1:p.Val9Leu
  • LRG_530t1:c.25G>T
  • LRG_530:g.5195G>T
  • NC_000014.8:g.65569033C>A
  • NM_002382.3:c.25G>T
  • NM_002382.4:c.25G>T
Protein change:
V9L
Links:
dbSNP: rs201743423
NCBI 1000 Genomes Browser:
rs201743423
Molecular consequence:
  • NM_001320415.2:c.-250G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001271068.2:c.25G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001271069.2:c.25G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002382.5:c.25G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_145112.3:c.25G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_145113.3:c.25G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_145114.3:c.25G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_197957.4:c.25G>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MedGen: C0027672

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000673604Ambry Geneticscriteria provided, single submitter
Uncertain significance
(Feb 27, 2020)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

MAX mutations cause hereditary and sporadic pheochromocytoma and paraganglioma.

Burnichon N, Cascón A, Schiavi F, Morales NP, Comino-Méndez I, Abermil N, Inglada-Pérez L, de Cubas AA, Amar L, Barontini M, de Quirós SB, Bertherat J, Bignon YJ, Blok MJ, Bobisse S, Borrego S, Castellano M, Chanson P, Chiara MD, Corssmit EP, Giacchè M, de Krijger RR, et al.

Clin Cancer Res. 2012 May 15;18(10):2828-37. doi: 10.1158/1078-0432.CCR-12-0160. Epub 2012 Mar 27.

PubMed [citation]
PMID:
22452945

Functional and in silico assessment of MAX variants of unknown significance.

Comino-Méndez I, Leandro-García LJ, Montoya G, Inglada-Pérez L, de Cubas AA, Currás-Freixes M, Tysoe C, Izatt L, Letón R, Gómez-Graña Á, Mancikova V, Apellániz-Ruiz M, Mannelli M, Schiavi F, Favier J, Gimenez-Roqueplo AP, Timmers HJ, Roncador G, Garcia JF, Rodríguez-Antona C, Robledo M, Cascón A.

J Mol Med (Berl). 2015 Nov;93(11):1247-55. doi: 10.1007/s00109-015-1306-y. Epub 2015 Jun 14.

PubMed [citation]
PMID:
26070438

Details of each submission

From Ambry Genetics, SCV000673604.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (2)

Description

The p.V9L variant (also known as c.25G>T), located in coding exon 1 of the MAX gene, results from a G to T substitution at nucleotide position 25. The valine at codon 9 is replaced by leucine, an amino acid with highly similar properties. This variant was reported in 1 of 1694 patients with pheochromocytoma or paraganglioma; this patient was a 13 year old male with a pheochromocytoma and a thoracoabdominal paraganglioma (Burnichon N et al. Clin. Cancer Res. 2012 May; 18(10):2828-37; Comino-Méndez I et al. J. Mol. Med. 2015 Nov; 93(11):1247-55). Additionally, in a Luciferase reporter assay, the alteration MAX p.V9L was found to have a minor impact on MYC’s E-box transcriptional activation (Comino-Méndez I et al. J. Mol. Med. 2015 Nov; 93(11):1247-55). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Nov 27, 2021

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