TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6266	19021;19022;19023	chr2:178729360;178729359;178729358	chr2:179594087;179594086;179594085
N2AB	5949	18070;18071;18072	chr2:178729360;178729359;178729358	chr2:179594087;179594086;179594085
N2A	5022	15289;15290;15291	chr2:178729360;178729359;178729358	chr2:179594087;179594086;179594085
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-46
• Domain position: 68
• Structural Position: 151
• Q(SASA): 0.4214
• 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	rs761009610	-0.714	None	N	0.105	0.057	0.0716867268079	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	8.93E-06	0
T/A	rs761009610	-0.714	None	N	0.105	0.057	0.0716867268079	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	1.30976E-04	0	0	0	None	0	0	0	0	0
T/A	rs761009610	-0.714	None	N	0.105	0.057	0.0716867268079	gnomAD-4.0.0	7.68805E-06	None	None	None	None	N	None	0	5.08595E-05	None	0	0	None	0	0	7.18085E-06	0	0
T/I	None	None	0.004	N	0.428	0.067	0.290590437066	gnomAD-4.0.0	1.59174E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85922E-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	0.0637	likely_benign	0.0648	benign	-0.915	Destabilizing	None	N	0.105	neutral	N	0.387448262	None	None	N
T/C	0.3354	likely_benign	0.3287	benign	-0.45	Destabilizing	0.356	N	0.555	neutral	None	None	None	None	N
T/D	0.347	ambiguous	0.3318	benign	-0.181	Destabilizing	0.072	N	0.511	neutral	None	None	None	None	N
T/E	0.2566	likely_benign	0.2551	benign	-0.195	Destabilizing	0.072	N	0.529	neutral	None	None	None	None	N
T/F	0.2099	likely_benign	0.2016	benign	-1.124	Destabilizing	0.214	N	0.605	neutral	None	None	None	None	N
T/G	0.1913	likely_benign	0.1819	benign	-1.15	Destabilizing	0.016	N	0.396	neutral	None	None	None	None	N
T/H	0.2745	likely_benign	0.2598	benign	-1.464	Destabilizing	0.628	D	0.532	neutral	None	None	None	None	N
T/I	0.1029	likely_benign	0.1016	benign	-0.382	Destabilizing	0.004	N	0.428	neutral	N	0.466815909	None	None	N
T/K	0.2196	likely_benign	0.2073	benign	-0.67	Destabilizing	0.072	N	0.528	neutral	None	None	None	None	N
T/L	0.0876	likely_benign	0.0872	benign	-0.382	Destabilizing	0.007	N	0.337	neutral	None	None	None	None	N
T/M	0.0847	likely_benign	0.0816	benign	0.074	Stabilizing	0.214	N	0.565	neutral	None	None	None	None	N
T/N	0.1255	likely_benign	0.1188	benign	-0.565	Destabilizing	0.055	N	0.483	neutral	N	0.489287337	None	None	N
T/P	0.2491	likely_benign	0.2044	benign	-0.529	Destabilizing	0.106	N	0.572	neutral	D	0.535771775	None	None	N
T/Q	0.2298	likely_benign	0.2206	benign	-0.778	Destabilizing	0.356	N	0.613	neutral	None	None	None	None	N
T/R	0.1599	likely_benign	0.1544	benign	-0.417	Destabilizing	0.136	N	0.606	neutral	None	None	None	None	N
T/S	0.0933	likely_benign	0.0921	benign	-0.875	Destabilizing	0.001	N	0.129	neutral	N	0.417731096	None	None	N
T/V	0.0945	likely_benign	0.0944	benign	-0.529	Destabilizing	None	N	0.119	neutral	None	None	None	None	N
T/W	0.596	likely_pathogenic	0.5442	ambiguous	-1.028	Destabilizing	0.864	D	0.547	neutral	None	None	None	None	N
T/Y	0.2583	likely_benign	0.2495	benign	-0.798	Destabilizing	0.356	N	0.568	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.