TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22932	69019;69020;69021	chr2:178577632;178577631;178577630	chr2:179442359;179442358;179442357
N2AB	21291	64096;64097;64098	chr2:178577632;178577631;178577630	chr2:179442359;179442358;179442357
N2A	20364	61315;61316;61317	chr2:178577632;178577631;178577630	chr2:179442359;179442358;179442357
N2B	13867	41824;41825;41826	chr2:178577632;178577631;178577630	chr2:179442359;179442358;179442357
Novex-1	13992	42199;42200;42201	chr2:178577632;178577631;178577630	chr2:179442359;179442358;179442357
Novex-2	14059	42400;42401;42402	chr2:178577632;178577631;178577630	chr2:179442359;179442358;179442357
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: Fn3-54
• Domain position: 92
• Structural Position: 124
• Q(SASA): 0.6623
• Predicted PPI site: I

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	None	None	0.914	N	0.411	0.179	0.201204373187	gnomAD-4.0.0	3.60097E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.93751E-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	0.251	likely_benign	0.2637	benign	-1.213	Destabilizing	0.914	D	0.386	neutral	N	0.502618496	None	None	I
T/C	0.7413	likely_pathogenic	0.7727	pathogenic	-0.849	Destabilizing	0.999	D	0.547	neutral	None	None	None	None	I
T/D	0.9102	likely_pathogenic	0.923	pathogenic	-0.82	Destabilizing	0.99	D	0.604	neutral	None	None	None	None	I
T/E	0.9097	likely_pathogenic	0.9282	pathogenic	-0.681	Destabilizing	0.98	D	0.605	neutral	None	None	None	None	I
T/F	0.904	likely_pathogenic	0.9225	pathogenic	-0.866	Destabilizing	0.997	D	0.541	neutral	None	None	None	None	I
T/G	0.5	ambiguous	0.5083	ambiguous	-1.601	Destabilizing	0.98	D	0.49	neutral	None	None	None	None	I
T/H	0.8919	likely_pathogenic	0.9102	pathogenic	-1.642	Destabilizing	0.997	D	0.521	neutral	None	None	None	None	I
T/I	0.7624	likely_pathogenic	0.7964	pathogenic	-0.216	Destabilizing	0.987	D	0.591	neutral	N	0.505327521	None	None	I
T/K	0.883	likely_pathogenic	0.8992	pathogenic	-0.657	Destabilizing	0.841	D	0.611	neutral	N	0.510380404	None	None	I
T/L	0.4377	ambiguous	0.4631	ambiguous	-0.216	Destabilizing	0.933	D	0.61	neutral	None	None	None	None	I
T/M	0.3073	likely_benign	0.3432	ambiguous	-0.126	Destabilizing	0.999	D	0.544	neutral	None	None	None	None	I
T/N	0.626	likely_pathogenic	0.6592	pathogenic	-1.032	Destabilizing	0.98	D	0.572	neutral	None	None	None	None	I
T/P	0.6241	likely_pathogenic	0.6364	pathogenic	-0.516	Destabilizing	0.996	D	0.571	neutral	N	0.496252621	None	None	I
T/Q	0.832	likely_pathogenic	0.8607	pathogenic	-0.966	Destabilizing	0.98	D	0.571	neutral	None	None	None	None	I
T/R	0.8428	likely_pathogenic	0.864	pathogenic	-0.673	Destabilizing	0.071	N	0.326	neutral	N	0.521990199	None	None	I
T/S	0.1881	likely_benign	0.1974	benign	-1.387	Destabilizing	0.914	D	0.411	neutral	N	0.446187134	None	None	I
T/V	0.5225	ambiguous	0.5526	ambiguous	-0.516	Destabilizing	0.966	D	0.553	neutral	None	None	None	None	I
T/W	0.9766	likely_pathogenic	0.9823	pathogenic	-0.836	Destabilizing	0.999	D	0.551	neutral	None	None	None	None	I
T/Y	0.941	likely_pathogenic	0.9549	pathogenic	-0.554	Destabilizing	0.997	D	0.534	neutral	None	None	None	None	I

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.