NM_002382.5(MAX):c.341A>C (p.Asn114Thr) AND Hereditary pheochromocytoma-paraganglioma

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 25, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000233307.12

Allele description [Variation Report for NM_002382.5(MAX):c.341A>C (p.Asn114Thr)]

NM_002382.5(MAX):c.341A>C (p.Asn114Thr)

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.341A>C (p.Asn114Thr)

HGVS:

NC_000014.9:g.65076618T>G
NG_029830.1:g.30892A>C
NM_001271069.2:c.144+17090A>C
NM_001320415.2:c.152A>C
NM_001407094.1:c.341A>C
NM_001407095.1:c.314A>C
NM_001407096.1:c.*114A>C
NM_001407097.1:c.*130A>C
NM_001407098.1:c.233A>C
NM_001407099.1:c.*114A>C
NM_001407100.1:c.*130A>C
NM_001407101.1:c.*130A>C
NM_001407102.1:c.*114A>C
NM_001407103.1:c.*130A>C
NM_001407104.1:c.*114A>C
NM_001407105.1:c.152A>C
NM_001407106.1:c.152A>C
NM_001407107.1:c.152A>C
NM_001407108.1:c.*114A>C
NM_001407109.1:c.*130A>C
NM_001407110.1:c.*130A>C
NM_001407111.1:c.140A>C
NM_001407112.1:c.140A>C
NM_002382.5:c.341A>CMANE SELECT
NM_145112.3:c.314A>C
NM_145113.3:c.*130A>C
NM_197957.4:c.171+17090A>C
NP_001307344.1:p.Asn51Thr
NP_001394023.1:p.Asn114Thr
NP_001394024.1:p.Asn105Thr
NP_001394027.1:p.Asn78Thr
NP_001394034.1:p.Asn51Thr
NP_001394035.1:p.Asn51Thr
NP_001394036.1:p.Asn51Thr
NP_001394040.1:p.Asn47Thr
NP_001394041.1:p.Asn47Thr
NP_002373.3:p.Asn114Thr
NP_002373.3:p.Asn114Thr
NP_660087.1:p.Asn105Thr
LRG_530t1:c.341A>C
LRG_530:g.30892A>C
LRG_530p1:p.Asn114Thr
NC_000014.8:g.65543336T>G
NM_002382.3:c.341A>C
NM_002382.4:c.341A>C
NR_073137.1:n.465A>C
NR_073137.2:n.465A>C
NR_176275.1:n.584A>C
NR_176278.1:n.314A>C
NR_176279.1:n.518A>C
NR_176280.1:n.483A>C
NR_176281.1:n.665A>C
NR_176282.1:n.388A>C

Protein change:

N105T

Links:

dbSNP: rs772912674

NCBI 1000 Genomes Browser:

rs772912674

Molecular consequence:

NM_145113.3:c.*130A>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001271069.2:c.144+17090A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_197957.4:c.171+17090A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001320415.2:c.152A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407094.1:c.341A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407095.1:c.314A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407098.1:c.233A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407105.1:c.152A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407106.1:c.152A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407107.1:c.152A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407111.1:c.140A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407112.1:c.140A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_002382.5:c.341A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_145112.3:c.314A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary pheochromocytoma-paraganglioma
Synonyms:: Hereditary Paraganglioma-Pheochromocytoma Syndromes; Hereditary Paragangliomas and Pheochromocytomas
Identifiers:: MONDO: MONDO:0017366; MedGen: C1708353

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000287376	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 25, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26070438, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000287376

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 25, 2024)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000287376.10

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces asparagine, which is neutral and polar, with threonine, which is neutral and polar, at codon 114 of the MAX protein (p.Asn114Thr). This variant is present in population databases (rs772912674, gnomAD 0.009%). This missense change has been observed in individual(s) with isolated paraganglioma (PMID: 26070438). This variant is also known as p.N105T. ClinVar contains an entry for this variant (Variation ID: 239150). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) indicates that this missense variant is not expected to disrupt MAX function with a negative predictive value of 95%. Experimental studies have shown that this missense change does not substantially affect MAX function (PMID: 26070438). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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