TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8846	26761;26762;26763	chr2:178714122;178714121;178714120	chr2:179578849;179578848;179578847
N2AB	8529	25810;25811;25812	chr2:178714122;178714121;178714120	chr2:179578849;179578848;179578847
N2A	7602	23029;23030;23031	chr2:178714122;178714121;178714120	chr2:179578849;179578848;179578847
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: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-74
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.5618
• 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/N	rs780494547	-0.391	0.642	N	0.285	0.163	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
T/S	None	None	0.01	N	0.103	0.044	0.146414634003	gnomAD-4.0.0	1.20034E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31252E-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	0.0755	likely_benign	0.0795	benign	-0.745	Destabilizing	0.27	N	0.248	neutral	N	0.451034728	None	None	N
T/C	0.4391	ambiguous	0.4422	ambiguous	-0.395	Destabilizing	0.995	D	0.36	neutral	None	None	None	None	N
T/D	0.401	ambiguous	0.4284	ambiguous	-0.055	Destabilizing	0.704	D	0.37	neutral	None	None	None	None	N
T/E	0.4094	ambiguous	0.4174	ambiguous	-0.069	Destabilizing	0.704	D	0.319	neutral	None	None	None	None	N
T/F	0.2072	likely_benign	0.232	benign	-0.89	Destabilizing	0.944	D	0.395	neutral	None	None	None	None	N
T/G	0.2353	likely_benign	0.2554	benign	-0.987	Destabilizing	0.543	D	0.331	neutral	None	None	None	None	N
T/H	0.2648	likely_benign	0.2993	benign	-1.262	Destabilizing	0.981	D	0.345	neutral	None	None	None	None	N
T/I	0.1344	likely_benign	0.1541	benign	-0.2	Destabilizing	0.01	N	0.141	neutral	N	0.50829352	None	None	N
T/K	0.3017	likely_benign	0.3227	benign	-0.641	Destabilizing	0.031	N	0.182	neutral	None	None	None	None	N
T/L	0.104	likely_benign	0.113	benign	-0.2	Destabilizing	0.329	N	0.339	neutral	None	None	None	None	N
T/M	0.0943	likely_benign	0.1023	benign	0.105	Stabilizing	0.176	N	0.281	neutral	None	None	None	None	N
T/N	0.1082	likely_benign	0.1225	benign	-0.529	Destabilizing	0.642	D	0.285	neutral	N	0.459691496	None	None	N
T/P	0.088	likely_benign	0.0961	benign	-0.349	Destabilizing	0.927	D	0.386	neutral	N	0.424405487	None	None	N
T/Q	0.2895	likely_benign	0.3086	benign	-0.704	Destabilizing	0.893	D	0.398	neutral	None	None	None	None	N
T/R	0.2262	likely_benign	0.2409	benign	-0.394	Destabilizing	0.543	D	0.369	neutral	None	None	None	None	N
T/S	0.0903	likely_benign	0.0991	benign	-0.819	Destabilizing	0.01	N	0.103	neutral	N	0.402912707	None	None	N
T/V	0.1218	likely_benign	0.1375	benign	-0.349	Destabilizing	0.329	N	0.283	neutral	None	None	None	None	N
T/W	0.6225	likely_pathogenic	0.6239	pathogenic	-0.825	Destabilizing	0.995	D	0.383	neutral	None	None	None	None	N
T/Y	0.2489	likely_benign	0.2622	benign	-0.591	Destabilizing	0.981	D	0.366	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.