TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24133	72622;72623;72624	chr2:178573735;178573734;178573733	chr2:179438462;179438461;179438460
N2AB	22492	67699;67700;67701	chr2:178573735;178573734;178573733	chr2:179438462;179438461;179438460
N2A	21565	64918;64919;64920	chr2:178573735;178573734;178573733	chr2:179438462;179438461;179438460
N2B	15068	45427;45428;45429	chr2:178573735;178573734;178573733	chr2:179438462;179438461;179438460
Novex-1	15193	45802;45803;45804	chr2:178573735;178573734;178573733	chr2:179438462;179438461;179438460
Novex-2	15260	46003;46004;46005	chr2:178573735;178573734;178573733	chr2:179438462;179438461;179438460
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: Fn3-63
• Domain position: 12
• Structural Position: 13
• Q(SASA): 0.535
• 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	rs977953337	None	0.497	N	0.589	0.352	0.443388199986	gnomAD-4.0.0	1.41993E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.83867E-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	0.0873	benign	-0.514	Destabilizing	0.055	N	0.39	neutral	N	0.511267615	None	None	N
T/C	0.234	likely_benign	0.3012	benign	-0.365	Destabilizing	0.909	D	0.64	neutral	None	None	None	None	N
T/D	0.2244	likely_benign	0.3157	benign	0.156	Stabilizing	0.157	N	0.589	neutral	None	None	None	None	N
T/E	0.2369	likely_benign	0.3052	benign	0.112	Stabilizing	0.157	N	0.593	neutral	None	None	None	None	N
T/F	0.1894	likely_benign	0.24	benign	-0.781	Destabilizing	0.726	D	0.693	prob.neutral	None	None	None	None	N
T/G	0.1148	likely_benign	0.1459	benign	-0.707	Destabilizing	0.157	N	0.591	neutral	None	None	None	None	N
T/H	0.2088	likely_benign	0.2382	benign	-0.96	Destabilizing	0.909	D	0.695	prob.neutral	None	None	None	None	N
T/I	0.1881	likely_benign	0.2325	benign	-0.114	Destabilizing	0.497	N	0.589	neutral	N	0.471421691	None	None	N
T/K	0.2208	likely_benign	0.2407	benign	-0.519	Destabilizing	0.157	N	0.589	neutral	None	None	None	None	N
T/L	0.0954	likely_benign	0.1111	benign	-0.114	Destabilizing	0.272	N	0.573	neutral	None	None	None	None	N
T/M	0.1	likely_benign	0.1103	benign	0.046	Stabilizing	0.968	D	0.645	neutral	None	None	None	None	N
T/N	0.0938	likely_benign	0.1129	benign	-0.353	Destabilizing	0.124	N	0.544	neutral	N	0.483791955	None	None	N
T/P	0.4224	ambiguous	0.4534	ambiguous	-0.216	Destabilizing	0.497	N	0.585	neutral	N	0.490477452	None	None	N
T/Q	0.2254	likely_benign	0.255	benign	-0.551	Destabilizing	0.567	D	0.64	neutral	None	None	None	None	N
T/R	0.201	likely_benign	0.2166	benign	-0.246	Destabilizing	0.567	D	0.621	neutral	None	None	None	None	N
T/S	0.0656	likely_benign	0.0764	benign	-0.616	Destabilizing	None	N	0.175	neutral	N	0.414236926	None	None	N
T/V	0.1458	likely_benign	0.1712	benign	-0.216	Destabilizing	0.272	N	0.512	neutral	None	None	None	None	N
T/W	0.4128	ambiguous	0.5049	ambiguous	-0.741	Destabilizing	0.968	D	0.77	deleterious	None	None	None	None	N
T/Y	0.1935	likely_benign	0.2523	benign	-0.489	Destabilizing	0.726	D	0.7	prob.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.