TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14319	43180;43181;43182	chr2:178633318;178633317;178633316	chr2:179498045;179498044;179498043
N2AB	12678	38257;38258;38259	chr2:178633318;178633317;178633316	chr2:179498045;179498044;179498043
N2A	11751	35476;35477;35478	chr2:178633318;178633317;178633316	chr2:179498045;179498044;179498043
N2B	5254	15985;15986;15987	chr2:178633318;178633317;178633316	chr2:179498045;179498044;179498043
Novex-1	5379	16360;16361;16362	chr2:178633318;178633317;178633316	chr2:179498045;179498044;179498043
Novex-2	5446	16561;16562;16563	chr2:178633318;178633317;178633316	chr2:179498045;179498044;179498043
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-94
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.1811
• 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
I/T	None	None	0.976	D	0.524	0.48	0.763395407181	gnomAD-4.0.0	1.36924E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.9976E-07	1.16255E-05	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
I/A	0.9529	likely_pathogenic	0.9308	pathogenic	-1.391	Destabilizing	0.982	D	0.412	neutral	None	None	None	None	I
I/C	0.9726	likely_pathogenic	0.961	pathogenic	-0.77	Destabilizing	1.0	D	0.448	neutral	None	None	None	None	I
I/D	0.995	likely_pathogenic	0.9945	pathogenic	-0.706	Destabilizing	0.999	D	0.742	deleterious	None	None	None	None	I
I/E	0.98	likely_pathogenic	0.9786	pathogenic	-0.737	Destabilizing	0.999	D	0.77	deleterious	None	None	None	None	I
I/F	0.6987	likely_pathogenic	0.6216	pathogenic	-1.106	Destabilizing	0.997	D	0.451	neutral	None	None	None	None	I
I/G	0.9867	likely_pathogenic	0.9832	pathogenic	-1.678	Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	I
I/H	0.9792	likely_pathogenic	0.9762	pathogenic	-0.989	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	I
I/K	0.9519	likely_pathogenic	0.9542	pathogenic	-0.878	Destabilizing	0.999	D	0.767	deleterious	D	0.674286585	None	None	I
I/L	0.3657	ambiguous	0.3321	benign	-0.698	Destabilizing	0.787	D	0.397	neutral	N	0.499551229	None	None	I
I/M	0.4336	ambiguous	0.3948	ambiguous	-0.483	Destabilizing	0.997	D	0.401	neutral	D	0.634703668	None	None	I
I/N	0.9384	likely_pathogenic	0.9307	pathogenic	-0.592	Destabilizing	0.999	D	0.733	deleterious	None	None	None	None	I
I/P	0.9424	likely_pathogenic	0.9213	pathogenic	-0.896	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	I
I/Q	0.9591	likely_pathogenic	0.957	pathogenic	-0.785	Destabilizing	0.999	D	0.686	prob.delet.	None	None	None	None	I
I/R	0.9275	likely_pathogenic	0.9305	pathogenic	-0.319	Destabilizing	0.999	D	0.733	deleterious	D	0.674286585	None	None	I
I/S	0.9468	likely_pathogenic	0.9344	pathogenic	-1.171	Destabilizing	0.997	D	0.654	prob.neutral	None	None	None	None	I
I/T	0.9236	likely_pathogenic	0.8847	pathogenic	-1.083	Destabilizing	0.976	D	0.524	neutral	D	0.672596082	None	None	I
I/V	0.2264	likely_benign	0.1658	benign	-0.896	Destabilizing	0.188	N	0.178	neutral	N	0.489474627	None	None	I
I/W	0.9795	likely_pathogenic	0.976	pathogenic	-1.16	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
I/Y	0.9463	likely_pathogenic	0.9322	pathogenic	-0.928	Destabilizing	0.999	D	0.383	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.