NM_002382.5(MAX):c.376G>T (p.Ala126Ser) AND Hereditary pheochromocytoma-paraganglioma

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 24, 2019
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:: RCV001044019.9

Allele description [Variation Report for NM_002382.5(MAX):c.376G>T (p.Ala126Ser)]

NM_002382.5(MAX):c.376G>T (p.Ala126Ser)

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.376G>T (p.Ala126Ser)

HGVS:

NC_000014.9:g.65076583C>A
NG_029830.1:g.30927G>T
NM_001271069.2:c.144+17125G>T
NM_001320415.2:c.187G>T
NM_001407094.1:c.376G>T
NM_001407095.1:c.349G>T
NM_001407096.1:c.*149G>T
NM_001407097.1:c.*165G>T
NM_001407098.1:c.268G>T
NM_001407099.1:c.*149G>T
NM_001407100.1:c.*165G>T
NM_001407101.1:c.*165G>T
NM_001407102.1:c.*149G>T
NM_001407103.1:c.*165G>T
NM_001407104.1:c.*149G>T
NM_001407105.1:c.187G>T
NM_001407106.1:c.187G>T
NM_001407107.1:c.187G>T
NM_001407108.1:c.*149G>T
NM_001407109.1:c.*165G>T
NM_001407110.1:c.*165G>T
NM_001407111.1:c.175G>T
NM_001407112.1:c.175G>T
NM_002382.5:c.376G>TMANE SELECT
NM_145112.3:c.349G>T
NM_145113.3:c.*165G>T
NM_197957.4:c.171+17125G>T
NP_001307344.1:p.Ala63Ser
NP_001394023.1:p.Ala126Ser
NP_001394024.1:p.Ala117Ser
NP_001394027.1:p.Ala90Ser
NP_001394034.1:p.Ala63Ser
NP_001394035.1:p.Ala63Ser
NP_001394036.1:p.Ala63Ser
NP_001394040.1:p.Ala59Ser
NP_001394041.1:p.Ala59Ser
NP_002373.3:p.Ala126Ser
NP_002373.3:p.Ala126Ser
NP_660087.1:p.Ala117Ser
LRG_530t1:c.376G>T
LRG_530:g.30927G>T
LRG_530p1:p.Ala126Ser
NC_000014.8:g.65543301C>A
NM_002382.3:c.376G>T
NM_002382.4:c.376G>T
NR_073137.1:n.500G>T
NR_073137.2:n.500G>T
NR_176275.1:n.619G>T
NR_176278.1:n.349G>T
NR_176279.1:n.553G>T
NR_176280.1:n.518G>T
NR_176281.1:n.700G>T
NR_176282.1:n.423G>T

Protein change:

A117S

Links:

dbSNP: rs779789251

NCBI 1000 Genomes Browser:

rs779789251

Molecular consequence:

NM_145113.3:c.*165G>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001271069.2:c.144+17125G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_197957.4:c.171+17125G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001320415.2:c.187G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407094.1:c.376G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407095.1:c.349G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407098.1:c.268G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407105.1:c.187G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407106.1:c.187G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407107.1:c.187G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407111.1:c.175G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407112.1:c.175G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_002382.5:c.376G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_145112.3:c.349G>T - 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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LOC126862611 [Homo sapiens]
LOC126862611 [Homo sapiens]
Gene ID:126862611

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001207792	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 24, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001207792

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 24, 2019)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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, SCV001207792.5

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

Description

Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. This variant has not been reported in the literature in individuals with MAX-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with serine at codon 126 of the MAX protein (p.Ala126Ser). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and serine.

#	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: Sep 29, 2024

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