ClinVar Miner

Submissions for variant NM_000075.4(CDK4):c.71G>A (p.Arg24His) (rs104894340)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001026151 SCV001188474 pathogenic Hereditary cancer-predisposing syndrome 2019-12-12 criteria provided, single submitter clinical testing The p.R24H pathogenic mutation (also known as c.71G>A), located in coding exon 1 of the CDK4 gene, results from a G to A substitution at nucleotide position 71. The arginine at codon 24 is replaced by histidine, an amino acid with highly similar properties. This alteration has been reported in multiple unrelated individuals with personal and/or family history consistent with familial melanoma, and has been shown to segregate with disease in multiple large Norwegian, French, and Australian kindreds (Soufir N et al. Hum. Mol. Genet., 1998 Feb;7:209-16; Molven A et al. Genes Chromosomes Cancer, 2005 Sep;44:10-8; Nikolaou V et al. Br. J. Dermatol., 2011 Dec;165:1219-22; Puntervoll HE et al. J. Med. Genet., 2013 Apr;50:264-70; Veinalde R et al. Melanoma Res., 2013 Jun;23:221-6; Karagianni F et al. Acta Derm. Venereol., 2018 Oct;98:862-866). Further, functional analyses of an alteration at the same codon, p.R24C, have shown reduced p16INK4A inhibition of CDK4 kinase activity and cell cycle progression (Bartkova J et al. Cancer Res., 1996 Dec;56:5475-83; Coleman KG et al. J. Biol. Chem., 1997 Jul;272:18869-74). This amino acid position is highly conserved in available vertebrate species. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
OMIM RCV000018437 SCV000038719 risk factor Cutaneous malignant melanoma 3 2005-09-01 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442005 SCV000505666 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423488 SCV000505667 likely pathogenic Melanoma 2015-07-14 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000434181 SCV000505668 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444499 SCV000505669 likely pathogenic Multiple myeloma 2016-05-31 no assertion criteria provided literature only

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