TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15586	46981;46982;46983	chr2:178618794;178618793;178618792	chr2:179483521;179483520;179483519
N2AB	13945	42058;42059;42060	chr2:178618794;178618793;178618792	chr2:179483521;179483520;179483519
N2A	13018	39277;39278;39279	chr2:178618794;178618793;178618792	chr2:179483521;179483520;179483519
N2B	6521	19786;19787;19788	chr2:178618794;178618793;178618792	chr2:179483521;179483520;179483519
Novex-1	6646	20161;20162;20163	chr2:178618794;178618793;178618792	chr2:179483521;179483520;179483519
Novex-2	6713	20362;20363;20364	chr2:178618794;178618793;178618792	chr2:179483521;179483520;179483519
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-108
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.3227
• 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/S	rs764917649	-0.767	0.98	N	0.512	0.138	0.143124449307	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.67504E-04
T/S	rs764917649	-0.767	0.98	N	0.512	0.138	0.143124449307	gnomAD-4.0.0	1.59713E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.04044E-05

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	0.1032	likely_benign	0.115	benign	-0.622	Destabilizing	0.91	D	0.479	neutral	N	0.460211243	None	None	N
T/C	0.4124	ambiguous	0.4225	ambiguous	-0.437	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	N
T/D	0.403	ambiguous	0.4204	ambiguous	0.149	Stabilizing	0.999	D	0.645	neutral	None	None	None	None	N
T/E	0.2516	likely_benign	0.278	benign	0.144	Stabilizing	0.999	D	0.64	neutral	None	None	None	None	N
T/F	0.2297	likely_benign	0.27	benign	-0.73	Destabilizing	0.996	D	0.714	prob.delet.	None	None	None	None	N
T/G	0.3413	ambiguous	0.3808	ambiguous	-0.866	Destabilizing	0.995	D	0.617	neutral	None	None	None	None	N
T/H	0.246	likely_benign	0.2655	benign	-1.076	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
T/I	0.1282	likely_benign	0.1484	benign	-0.072	Destabilizing	0.925	D	0.572	neutral	N	0.457543516	None	None	N
T/K	0.2172	likely_benign	0.2383	benign	-0.577	Destabilizing	0.998	D	0.642	neutral	N	0.456446007	None	None	N
T/L	0.0966	likely_benign	0.1073	benign	-0.072	Destabilizing	0.871	D	0.545	neutral	None	None	None	None	N
T/M	0.0905	likely_benign	0.1039	benign	0.007	Stabilizing	0.996	D	0.703	prob.neutral	None	None	None	None	N
T/N	0.134	likely_benign	0.1437	benign	-0.5	Destabilizing	0.999	D	0.579	neutral	None	None	None	None	N
T/P	0.3321	likely_benign	0.3364	benign	-0.223	Destabilizing	0.998	D	0.695	prob.neutral	N	0.462024896	None	None	N
T/Q	0.2032	likely_benign	0.2223	benign	-0.613	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
T/R	0.1907	likely_benign	0.2148	benign	-0.372	Destabilizing	0.998	D	0.695	prob.neutral	N	0.452189505	None	None	N
T/S	0.1261	likely_benign	0.1459	benign	-0.789	Destabilizing	0.98	D	0.512	neutral	N	0.457228874	None	None	N
T/V	0.1046	likely_benign	0.1184	benign	-0.223	Destabilizing	0.155	N	0.245	neutral	None	None	None	None	N
T/W	0.5693	likely_pathogenic	0.6032	pathogenic	-0.698	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
T/Y	0.258	likely_benign	0.2687	benign	-0.445	Destabilizing	0.999	D	0.718	prob.delet.	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.