NM_000075.4(CDK4):c.122A>G (p.Asn41Ser) AND Hereditary melanoma

Clinical significance:Uncertain significance (Last evaluated: Oct 29, 2020)

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_000075.4(CDK4):c.122A>G (p.Asn41Ser)]

NM_000075.4(CDK4):c.122A>G (p.Asn41Ser)

CDK4:cyclin dependent kinase 4 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000075.4(CDK4):c.122A>G (p.Asn41Ser)
  • NC_000012.12:g.57751596T>C
  • NG_007484.2:g.5786A>G
  • NM_000075.4:c.122A>GMANE SELECT
  • NP_000066.1:p.Asn41Ser
  • LRG_490t1:c.122A>G
  • LRG_490:g.5786A>G
  • NC_000012.11:g.58145379T>C
  • NM_000075.2:c.122A>G
  • NM_000075.3:c.122A>G
  • P11802:p.Asn41Ser
Protein change:
UniProtKB: P11802#VAR_021152; dbSNP: rs144890720
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000075.4:c.122A>G - missense variant - [Sequence Ontology: SO:0001583]


Hereditary melanoma
Hereditary cutaneous melanoma; Familial melanoma
MONDO: MONDO:0018961; MedGen: C1512419

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000166198Invitaecriteria provided, single submitter
Uncertain significance
(Oct 29, 2020)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Summary from all submissions

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



Pathogenic variant burden in the ExAC database: an empirical approach to evaluating population data for clinical variant interpretation.

Kobayashi Y, Yang S, Nykamp K, Garcia J, Lincoln SE, Topper SE.

Genome Med. 2017 Feb 6;9(1):13. doi: 10.1186/s13073-017-0403-7.

PubMed [citation]

Complete scanning of the CDK4 gene by denaturing gradient gel electrophoresis: a novel missense mutation but low overall frequency of mutations in sporadic metastatic malignant melanoma.

Guldberg P, Kirkin AF, Gronbaek K, thor Straten P, Ahrenkiel V, Zeuthen J.

Int J Cancer. 1997 Sep 4;72(5):780-3.

PubMed [citation]
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV000166198.9

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)


This sequence change replaces asparagine with serine at codon 41 of the CDK4 protein (p.Asn41Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs144890720, ExAC 0.03%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in individuals affected with melanoma, breast cancer, colorectal cancer, and suspected Lynch syndrome (PMID: 9311594, 25186627, 25980754, 28135145). ClinVar contains an entry for this variant (Variation ID: 135822). 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.

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

Last Updated: Nov 6, 2021

Support Center