TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19417	58474;58475;58476	chr2:178594144;178594143;178594142	chr2:179458871;179458870;179458869
N2AB	17776	53551;53552;53553	chr2:178594144;178594143;178594142	chr2:179458871;179458870;179458869
N2A	16849	50770;50771;50772	chr2:178594144;178594143;178594142	chr2:179458871;179458870;179458869
N2B	10352	31279;31280;31281	chr2:178594144;178594143;178594142	chr2:179458871;179458870;179458869
Novex-1	10477	31654;31655;31656	chr2:178594144;178594143;178594142	chr2:179458871;179458870;179458869
Novex-2	10544	31855;31856;31857	chr2:178594144;178594143;178594142	chr2:179458871;179458870;179458869
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-118
• Domain position: 27
• Structural Position: 45
• Q(SASA): 0.8721
• Predicted PPI site: I

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	rs2050890931	None	0.134	N	0.23	0.26	0.31291088546	gnomAD-4.0.0	1.5921E-06	None	None	None	None	I	None	5.65739E-05	0	None	0	0	None	0	0	0	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	0.1598	likely_benign	0.1693	benign	-0.112	Destabilizing	0.079	N	0.193	neutral	None	None	None	None	I
K/C	0.4665	ambiguous	0.5007	ambiguous	-0.261	Destabilizing	0.999	D	0.458	neutral	None	None	None	None	I
K/D	0.3425	ambiguous	0.3536	ambiguous	0.099	Stabilizing	0.939	D	0.495	neutral	None	None	None	None	I
K/E	0.1097	likely_benign	0.1131	benign	0.156	Stabilizing	0.92	D	0.433	neutral	N	0.466082404	None	None	I
K/F	0.5542	ambiguous	0.5627	ambiguous	-0.022	Destabilizing	0.997	D	0.483	neutral	None	None	None	None	I
K/G	0.313	likely_benign	0.3376	benign	-0.397	Destabilizing	0.863	D	0.439	neutral	None	None	None	None	I
K/H	0.2108	likely_benign	0.2104	benign	-0.653	Destabilizing	0.997	D	0.471	neutral	None	None	None	None	I
K/I	0.1698	likely_benign	0.1671	benign	0.583	Stabilizing	0.982	D	0.489	neutral	None	None	None	None	I
K/L	0.2095	likely_benign	0.2142	benign	0.583	Stabilizing	0.939	D	0.477	neutral	None	None	None	None	I
K/M	0.1369	likely_benign	0.1477	benign	0.263	Stabilizing	0.996	D	0.479	neutral	D	0.523517341	None	None	I
K/N	0.2272	likely_benign	0.2264	benign	0.023	Stabilizing	0.92	D	0.486	neutral	D	0.522477191	None	None	I
K/P	0.8282	likely_pathogenic	0.8495	pathogenic	0.382	Stabilizing	0.969	D	0.51	neutral	None	None	None	None	I
K/Q	0.1002	likely_benign	0.099	benign	-0.073	Destabilizing	0.988	D	0.491	neutral	N	0.495578591	None	None	I
K/R	0.0785	likely_benign	0.0806	benign	-0.236	Destabilizing	0.959	D	0.453	neutral	N	0.499138972	None	None	I
K/S	0.1981	likely_benign	0.2096	benign	-0.507	Destabilizing	0.373	N	0.177	neutral	None	None	None	None	I
K/T	0.0763	likely_benign	0.0797	benign	-0.274	Destabilizing	0.134	N	0.23	neutral	N	0.441880179	None	None	I
K/V	0.1405	likely_benign	0.1421	benign	0.382	Stabilizing	0.939	D	0.467	neutral	None	None	None	None	I
K/W	0.6431	likely_pathogenic	0.6661	pathogenic	0.005	Stabilizing	0.999	D	0.485	neutral	None	None	None	None	I
K/Y	0.4838	ambiguous	0.4999	ambiguous	0.317	Stabilizing	0.997	D	0.495	neutral	None	None	None	None	I

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.