TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16573	49942;49943;49944	chr2:178613004;178613003;178613002	chr2:179477731;179477730;179477729
N2AB	14932	45019;45020;45021	chr2:178613004;178613003;178613002	chr2:179477731;179477730;179477729
N2A	14005	42238;42239;42240	chr2:178613004;178613003;178613002	chr2:179477731;179477730;179477729
N2B	7508	22747;22748;22749	chr2:178613004;178613003;178613002	chr2:179477731;179477730;179477729
Novex-1	7633	23122;23123;23124	chr2:178613004;178613003;178613002	chr2:179477731;179477730;179477729
Novex-2	7700	23323;23324;23325	chr2:178613004;178613003;178613002	chr2:179477731;179477730;179477729
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: Fn3-8
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.4896
• 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/P	None	None	0.997	D	0.745	0.496	0.401753679984	gnomAD-4.0.0	1.59337E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86187E-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	0.1163	likely_benign	0.1081	benign	-0.779	Destabilizing	0.76	D	0.483	neutral	N	0.484846742	None	None	N
T/C	0.5235	ambiguous	0.478	ambiguous	-0.478	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
T/D	0.4534	ambiguous	0.4998	ambiguous	-0.134	Destabilizing	0.986	D	0.711	prob.delet.	None	None	None	None	N
T/E	0.3346	likely_benign	0.3924	ambiguous	-0.122	Destabilizing	0.986	D	0.705	prob.neutral	None	None	None	None	N
T/F	0.3657	ambiguous	0.3709	ambiguous	-0.824	Destabilizing	0.986	D	0.769	deleterious	None	None	None	None	N
T/G	0.2551	likely_benign	0.2218	benign	-1.05	Destabilizing	0.953	D	0.67	neutral	None	None	None	None	N
T/H	0.3282	likely_benign	0.3467	ambiguous	-1.298	Destabilizing	0.999	D	0.76	deleterious	None	None	None	None	N
T/I	0.2423	likely_benign	0.2209	benign	-0.148	Destabilizing	0.964	D	0.715	prob.delet.	N	0.473495392	None	None	N
T/K	0.2408	likely_benign	0.3286	benign	-0.743	Destabilizing	0.982	D	0.702	prob.neutral	N	0.46905425	None	None	N
T/L	0.1119	likely_benign	0.1038	benign	-0.148	Destabilizing	0.06	N	0.378	neutral	None	None	None	None	N
T/M	0.1074	likely_benign	0.1026	benign	0.023	Stabilizing	0.986	D	0.74	deleterious	None	None	None	None	N
T/N	0.131	likely_benign	0.1213	benign	-0.687	Destabilizing	0.986	D	0.599	neutral	None	None	None	None	N
T/P	0.2244	likely_benign	0.2486	benign	-0.326	Destabilizing	0.997	D	0.745	deleterious	D	0.564461011	None	None	N
T/Q	0.226	likely_benign	0.2459	benign	-0.78	Destabilizing	0.993	D	0.745	deleterious	None	None	None	None	N
T/R	0.2143	likely_benign	0.3193	benign	-0.553	Destabilizing	0.991	D	0.745	deleterious	N	0.478021922	None	None	N
T/S	0.135	likely_benign	0.116	benign	-0.958	Destabilizing	0.374	N	0.409	neutral	N	0.467041343	None	None	N
T/V	0.1834	likely_benign	0.1594	benign	-0.326	Destabilizing	0.91	D	0.473	neutral	None	None	None	None	N
T/W	0.6939	likely_pathogenic	0.7451	pathogenic	-0.795	Destabilizing	0.999	D	0.743	deleterious	None	None	None	None	N
T/Y	0.4301	ambiguous	0.47	ambiguous	-0.557	Destabilizing	0.998	D	0.774	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.