NM_002382.5(MAX):c.344A>G (p.Tyr115Cys) AND Hereditary Paraganglioma-Pheochromocytoma Syndromes

Clinical significance:Uncertain significance (Last evaluated: Jun 21, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_002382.5(MAX):c.344A>G (p.Tyr115Cys)]

NM_002382.5(MAX):c.344A>G (p.Tyr115Cys)

MAX:MYC associated factor X [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_002382.5(MAX):c.344A>G (p.Tyr115Cys)
  • NC_000014.9:g.65076615T>C
  • NG_029830.1:g.30895A>G
  • NM_001271069.1:c.144+17093A>G
  • NM_001320415.2:c.155A>G
  • NM_002382.5:c.344A>GMANE SELECT
  • NM_145112.3:c.317A>G
  • NM_145113.3:c.*133A>G
  • NM_197957.3:c.171+17093A>G
  • NP_001307344.1:p.Tyr52Cys
  • NP_002373.3:p.Tyr115Cys
  • NP_660087.1:p.Tyr106Cys
  • LRG_530:g.30895A>G
  • NC_000014.8:g.65543333T>C
  • NM_002382.4:c.344A>G
  • NR_073137.1:n.468A>G
Protein change:
Molecular consequence:
  • NM_145113.3:c.*133A>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001271069.1:c.144+17093A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_197957.3:c.171+17093A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001320415.2:c.155A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002382.5:c.344A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_145112.3:c.317A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_073137.1:n.468A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]


Hereditary Paraganglioma-Pheochromocytoma Syndromes (PGL-PCC)
Hereditary Paragangliomas and Pheochromocytomas
MONDO: MONDO:0017366; MedGen: C1708353

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV001378023Invitaecriteria provided, single submitter
Uncertain significance
(Jun 21, 2019)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing



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):240-242.

PubMed [citation]

Details of each submission

From Invitae, SCV001378023.1

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


This sequence change replaces tyrosine with cysteine at codon 115 of the MAX protein (p.Tyr115Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with MAX-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but 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.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 19, 2020

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