TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27219	81880;81881;81882	chr2:178564477;178564476;178564475	chr2:179429204;179429203;179429202
N2AB	25578	76957;76958;76959	chr2:178564477;178564476;178564475	chr2:179429204;179429203;179429202
N2A	24651	74176;74177;74178	chr2:178564477;178564476;178564475	chr2:179429204;179429203;179429202
N2B	18154	54685;54686;54687	chr2:178564477;178564476;178564475	chr2:179429204;179429203;179429202
Novex-1	18279	55060;55061;55062	chr2:178564477;178564476;178564475	chr2:179429204;179429203;179429202
Novex-2	18346	55261;55262;55263	chr2:178564477;178564476;178564475	chr2:179429204;179429203;179429202
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-86
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.3011
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
K/T	None	None	0.997	N	0.71	0.452	0.327686398923	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
K/A	0.9745	likely_pathogenic	0.9714	pathogenic	-0.462	Destabilizing	0.983	D	0.572	neutral	None	None	None	None	N
K/C	0.9901	likely_pathogenic	0.9898	pathogenic	-0.542	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
K/D	0.9947	likely_pathogenic	0.9941	pathogenic	0.355	Stabilizing	0.998	D	0.769	deleterious	None	None	None	None	N
K/E	0.9653	likely_pathogenic	0.9587	pathogenic	0.443	Stabilizing	0.977	D	0.496	neutral	N	0.503914781	None	None	N
K/F	0.9959	likely_pathogenic	0.9951	pathogenic	-0.301	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
K/G	0.987	likely_pathogenic	0.9848	pathogenic	-0.776	Destabilizing	0.998	D	0.679	prob.neutral	None	None	None	None	N
K/H	0.9103	likely_pathogenic	0.9032	pathogenic	-0.998	Destabilizing	0.999	D	0.766	deleterious	None	None	None	None	N
K/I	0.966	likely_pathogenic	0.9559	pathogenic	0.326	Stabilizing	0.997	D	0.785	deleterious	N	0.478548034	None	None	N
K/L	0.9293	likely_pathogenic	0.9161	pathogenic	0.326	Stabilizing	0.995	D	0.679	prob.neutral	None	None	None	None	N
K/M	0.9076	likely_pathogenic	0.8875	pathogenic	0.106	Stabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
K/N	0.9869	likely_pathogenic	0.9836	pathogenic	-0.153	Destabilizing	0.993	D	0.668	neutral	N	0.474268847	None	None	N
K/P	0.9633	likely_pathogenic	0.9579	pathogenic	0.094	Stabilizing	0.999	D	0.772	deleterious	None	None	None	None	N
K/Q	0.8013	likely_pathogenic	0.7772	pathogenic	-0.233	Destabilizing	0.993	D	0.649	neutral	D	0.524426126	None	None	N
K/R	0.148	likely_benign	0.1406	benign	-0.298	Destabilizing	0.235	N	0.303	neutral	N	0.47638425	None	None	N
K/S	0.9901	likely_pathogenic	0.9877	pathogenic	-0.863	Destabilizing	0.983	D	0.574	neutral	None	None	None	None	N
K/T	0.9485	likely_pathogenic	0.9372	pathogenic	-0.573	Destabilizing	0.997	D	0.71	prob.delet.	N	0.502549344	None	None	N
K/V	0.9526	likely_pathogenic	0.9423	pathogenic	0.094	Stabilizing	0.998	D	0.756	deleterious	None	None	None	None	N
K/W	0.9926	likely_pathogenic	0.9912	pathogenic	-0.173	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
K/Y	0.9851	likely_pathogenic	0.9828	pathogenic	0.125	Stabilizing	0.999	D	0.764	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.