TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6847	20764;20765;20766	chr2:178725783;178725782;178725781	chr2:179590510;179590509;179590508
N2AB	6530	19813;19814;19815	chr2:178725783;178725782;178725781	chr2:179590510;179590509;179590508
N2A	5603	17032;17033;17034	chr2:178725783;178725782;178725781	chr2:179590510;179590509;179590508
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-52
• Domain position: 87
• Structural Position: 173
• Q(SASA): 0.145
• 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	rs1162932422	-1.055	None	N	0.216	0.066	0.0806252709748	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
T/S	rs1162932422	-1.055	None	N	0.216	0.066	0.0806252709748	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/S	rs1162932422	-1.055	None	N	0.216	0.066	0.0806252709748	gnomAD-4.0.0	2.60029E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.86386E-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
T/A	0.0667	likely_benign	0.0615	benign	-1.016	Destabilizing	None	N	0.234	neutral	N	0.515473861	None	None	N
T/C	0.3099	likely_benign	0.2774	benign	-0.781	Destabilizing	0.676	D	0.618	neutral	None	None	None	None	N
T/D	0.2506	likely_benign	0.2406	benign	-0.817	Destabilizing	0.072	N	0.619	neutral	None	None	None	None	N
T/E	0.2048	likely_benign	0.196	benign	-0.71	Destabilizing	0.016	N	0.597	neutral	None	None	None	None	N
T/F	0.1285	likely_benign	0.1187	benign	-0.717	Destabilizing	0.214	N	0.648	neutral	None	None	None	None	N
T/G	0.1921	likely_benign	0.168	benign	-1.379	Destabilizing	None	N	0.451	neutral	None	None	None	None	N
T/H	0.1588	likely_benign	0.155	benign	-1.541	Destabilizing	0.356	N	0.614	neutral	None	None	None	None	N
T/I	0.0939	likely_benign	0.0883	benign	-0.103	Destabilizing	None	N	0.477	neutral	D	0.528288443	None	None	N
T/K	0.1423	likely_benign	0.1418	benign	-0.835	Destabilizing	0.016	N	0.596	neutral	None	None	None	None	N
T/L	0.0673	likely_benign	0.0663	benign	-0.103	Destabilizing	0.006	N	0.575	neutral	None	None	None	None	N
T/M	0.0762	likely_benign	0.0719	benign	-0.01	Destabilizing	0.214	N	0.627	neutral	None	None	None	None	N
T/N	0.0887	likely_benign	0.0848	benign	-1.127	Destabilizing	0.029	N	0.531	neutral	D	0.536137135	None	None	N
T/P	0.1295	likely_benign	0.1103	benign	-0.374	Destabilizing	0.055	N	0.663	neutral	N	0.50437015	None	None	N
T/Q	0.1642	likely_benign	0.1584	benign	-1.091	Destabilizing	0.003	N	0.485	neutral	None	None	None	None	N
T/R	0.1025	likely_benign	0.1124	benign	-0.798	Destabilizing	None	N	0.478	neutral	None	None	None	None	N
T/S	0.0825	likely_benign	0.0761	benign	-1.398	Destabilizing	None	N	0.216	neutral	N	0.455385407	None	None	N
T/V	0.0871	likely_benign	0.0806	benign	-0.374	Destabilizing	0.006	N	0.471	neutral	None	None	None	None	N
T/W	0.3924	ambiguous	0.3601	ambiguous	-0.73	Destabilizing	0.864	D	0.629	neutral	None	None	None	None	N
T/Y	0.1668	likely_benign	0.1551	benign	-0.451	Destabilizing	0.356	N	0.645	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.