TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35614	107065;107066;107067	chr2:178528911;178528910;178528909	chr2:179393638;179393637;179393636
N2AB	33973	102142;102143;102144	chr2:178528911;178528910;178528909	chr2:179393638;179393637;179393636
N2A	33046	99361;99362;99363	chr2:178528911;178528910;178528909	chr2:179393638;179393637;179393636
N2B	26549	79870;79871;79872	chr2:178528911;178528910;178528909	chr2:179393638;179393637;179393636
Novex-1	26674	80245;80246;80247	chr2:178528911;178528910;178528909	chr2:179393638;179393637;179393636
Novex-2	26741	80446;80447;80448	chr2:178528911;178528910;178528909	chr2:179393638;179393637;179393636
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-167
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.5324
• 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	rs2154131436	None	0.046	N	0.187	0.114	0.200317383148	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
T/A	0.1057	likely_benign	0.1016	benign	-0.705	Destabilizing	0.64	D	0.299	neutral	N	0.478531626	None	None	N
T/C	0.705	likely_pathogenic	0.6666	pathogenic	-0.351	Destabilizing	0.999	D	0.385	neutral	None	None	None	None	N
T/D	0.4563	ambiguous	0.4506	ambiguous	-0.106	Destabilizing	0.919	D	0.326	neutral	None	None	None	None	N
T/E	0.3823	ambiguous	0.3521	ambiguous	-0.132	Destabilizing	0.919	D	0.343	neutral	None	None	None	None	N
T/F	0.4451	ambiguous	0.4125	ambiguous	-0.911	Destabilizing	0.988	D	0.519	neutral	None	None	None	None	N
T/G	0.2734	likely_benign	0.2729	benign	-0.927	Destabilizing	0.851	D	0.383	neutral	None	None	None	None	N
T/H	0.353	ambiguous	0.3302	benign	-1.168	Destabilizing	0.999	D	0.511	neutral	None	None	None	None	N
T/I	0.3547	ambiguous	0.3105	benign	-0.215	Destabilizing	0.984	D	0.339	neutral	N	0.479398418	None	None	N
T/K	0.2627	likely_benign	0.2287	benign	-0.665	Destabilizing	0.919	D	0.329	neutral	None	None	None	None	N
T/L	0.192	likely_benign	0.169	benign	-0.215	Destabilizing	0.919	D	0.323	neutral	None	None	None	None	N
T/M	0.1867	likely_benign	0.1629	benign	0.029	Stabilizing	0.999	D	0.349	neutral	None	None	None	None	N
T/N	0.1505	likely_benign	0.1543	benign	-0.495	Destabilizing	0.896	D	0.285	neutral	N	0.478704984	None	None	N
T/P	0.1336	likely_benign	0.1277	benign	-0.347	Destabilizing	0.984	D	0.341	neutral	N	0.479225059	None	None	N
T/Q	0.294	likely_benign	0.2645	benign	-0.665	Destabilizing	0.988	D	0.339	neutral	None	None	None	None	N
T/R	0.2262	likely_benign	0.1936	benign	-0.381	Destabilizing	0.976	D	0.35	neutral	None	None	None	None	N
T/S	0.1096	likely_benign	0.1134	benign	-0.741	Destabilizing	0.046	N	0.187	neutral	N	0.458732357	None	None	N
T/V	0.2631	likely_benign	0.2351	benign	-0.347	Destabilizing	0.919	D	0.271	neutral	None	None	None	None	N
T/W	0.7915	likely_pathogenic	0.7659	pathogenic	-0.875	Destabilizing	0.999	D	0.609	neutral	None	None	None	None	N
T/Y	0.4478	ambiguous	0.4234	ambiguous	-0.642	Destabilizing	0.996	D	0.52	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.