TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14152	42679;42680;42681	chr2:178634045;178634044;178634043	chr2:179498772;179498771;179498770
N2AB	12511	37756;37757;37758	chr2:178634045;178634044;178634043	chr2:179498772;179498771;179498770
N2A	11584	34975;34976;34977	chr2:178634045;178634044;178634043	chr2:179498772;179498771;179498770
N2B	5087	15484;15485;15486	chr2:178634045;178634044;178634043	chr2:179498772;179498771;179498770
Novex-1	5212	15859;15860;15861	chr2:178634045;178634044;178634043	chr2:179498772;179498771;179498770
Novex-2	5279	16060;16061;16062	chr2:178634045;178634044;178634043	chr2:179498772;179498771;179498770
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-92
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.5901
• 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
T/A	rs1472786496	-0.093	0.999	D	0.48	0.453	0.438170831126	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
T/A	rs1472786496	-0.093	0.999	D	0.48	0.453	0.438170831126	gnomAD-4.0.0	1.5927E-06	None	None	None	None	N	None	5.66701E-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
T/A	0.1278	likely_benign	0.1307	benign	-0.405	Destabilizing	0.999	D	0.48	neutral	D	0.574838035	None	None	N
T/C	0.6185	likely_pathogenic	0.6295	pathogenic	-0.411	Destabilizing	1.0	D	0.578	neutral	None	None	None	None	N
T/D	0.469	ambiguous	0.4971	ambiguous	0.127	Stabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
T/E	0.275	likely_benign	0.3027	benign	0.111	Stabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
T/F	0.3413	ambiguous	0.3424	ambiguous	-0.568	Destabilizing	1.0	D	0.64	neutral	None	None	None	None	N
T/G	0.5334	ambiguous	0.5586	ambiguous	-0.627	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	N
T/H	0.3333	likely_benign	0.3608	ambiguous	-0.843	Destabilizing	1.0	D	0.571	neutral	None	None	None	None	N
T/I	0.1468	likely_benign	0.138	benign	0.077	Stabilizing	1.0	D	0.687	prob.neutral	D	0.579104188	None	None	N
T/K	0.2191	likely_benign	0.2578	benign	-0.544	Destabilizing	1.0	D	0.708	prob.delet.	N	0.496484528	None	None	N
T/L	0.1331	likely_benign	0.1326	benign	0.077	Stabilizing	0.999	D	0.649	neutral	None	None	None	None	N
T/M	0.0947	likely_benign	0.0929	benign	0.029	Stabilizing	1.0	D	0.594	neutral	None	None	None	None	N
T/N	0.1664	likely_benign	0.175	benign	-0.458	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
T/P	0.3405	ambiguous	0.3952	ambiguous	-0.051	Destabilizing	1.0	D	0.67	neutral	D	0.660008444	None	None	N
T/Q	0.2583	likely_benign	0.2835	benign	-0.569	Destabilizing	1.0	D	0.668	neutral	None	None	None	None	N
T/R	0.1983	likely_benign	0.2227	benign	-0.323	Destabilizing	1.0	D	0.667	neutral	N	0.501267539	None	None	N
T/S	0.1913	likely_benign	0.1932	benign	-0.687	Destabilizing	0.999	D	0.499	neutral	N	0.50306955	None	None	N
T/V	0.1307	likely_benign	0.13	benign	-0.051	Destabilizing	0.999	D	0.562	neutral	None	None	None	None	N
T/W	0.6963	likely_pathogenic	0.7128	pathogenic	-0.586	Destabilizing	1.0	D	0.609	neutral	None	None	None	None	N
T/Y	0.3601	ambiguous	0.3911	ambiguous	-0.315	Destabilizing	1.0	D	0.619	neutral	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.