TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14234	42925;42926;42927	chr2:178633659;178633658;178633657	chr2:179498386;179498385;179498384
N2AB	12593	38002;38003;38004	chr2:178633659;178633658;178633657	chr2:179498386;179498385;179498384
N2A	11666	35221;35222;35223	chr2:178633659;178633658;178633657	chr2:179498386;179498385;179498384
N2B	5169	15730;15731;15732	chr2:178633659;178633658;178633657	chr2:179498386;179498385;179498384
Novex-1	5294	16105;16106;16107	chr2:178633659;178633658;178633657	chr2:179498386;179498385;179498384
Novex-2	5361	16306;16307;16308	chr2:178633659;178633658;178633657	chr2:179498386;179498385;179498384
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-93
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.2892
• 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/I	None	None	1.0	N	0.751	0.464	0.333906830038	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	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	0.1434	likely_benign	0.1567	benign	-0.826	Destabilizing	0.999	D	0.494	neutral	N	0.486262267	None	None	N
T/C	0.6399	likely_pathogenic	0.695	pathogenic	-0.442	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	N
T/D	0.6638	likely_pathogenic	0.7244	pathogenic	0.125	Stabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
T/E	0.469	ambiguous	0.5409	ambiguous	0.177	Stabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
T/F	0.4512	ambiguous	0.4758	ambiguous	-0.74	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
T/G	0.4963	ambiguous	0.5566	ambiguous	-1.123	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
T/H	0.4431	ambiguous	0.513	ambiguous	-1.187	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
T/I	0.1832	likely_benign	0.1936	benign	-0.11	Destabilizing	1.0	D	0.751	deleterious	N	0.443656497	None	None	N
T/K	0.279	likely_benign	0.339	benign	-0.468	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
T/L	0.1216	likely_benign	0.1383	benign	-0.11	Destabilizing	0.999	D	0.675	prob.neutral	None	None	None	None	N
T/M	0.118	likely_benign	0.1208	benign	-0.048	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
T/N	0.2484	likely_benign	0.2776	benign	-0.569	Destabilizing	1.0	D	0.757	deleterious	D	0.589138302	None	None	N
T/P	0.3615	ambiguous	0.4073	ambiguous	-0.316	Destabilizing	1.0	D	0.743	deleterious	D	0.627693261	None	None	N
T/Q	0.3432	ambiguous	0.4066	ambiguous	-0.601	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
T/R	0.2437	likely_benign	0.2876	benign	-0.322	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
T/S	0.2037	likely_benign	0.222	benign	-0.923	Destabilizing	0.999	D	0.486	neutral	N	0.453139732	None	None	N
T/V	0.1497	likely_benign	0.1599	benign	-0.316	Destabilizing	0.999	D	0.59	neutral	None	None	None	None	N
T/W	0.7978	likely_pathogenic	0.8471	pathogenic	-0.703	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
T/Y	0.5133	ambiguous	0.5727	pathogenic	-0.44	Destabilizing	1.0	D	0.765	deleterious	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.