TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19599	59020;59021;59022	chr2:178593413;178593412;178593411	chr2:179458140;179458139;179458138
N2AB	17958	54097;54098;54099	chr2:178593413;178593412;178593411	chr2:179458140;179458139;179458138
N2A	17031	51316;51317;51318	chr2:178593413;178593412;178593411	chr2:179458140;179458139;179458138
N2B	10534	31825;31826;31827	chr2:178593413;178593412;178593411	chr2:179458140;179458139;179458138
Novex-1	10659	32200;32201;32202	chr2:178593413;178593412;178593411	chr2:179458140;179458139;179458138
Novex-2	10726	32401;32402;32403	chr2:178593413;178593412;178593411	chr2:179458140;179458139;179458138
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: Fn3-30
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.2325
• 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	rs367816473	0.193	0.002	D	0.349	0.16	None	gnomAD-2.1.1	4.29E-05	None	None	None	None	N	None	4.54921E-04	2.84E-05	None	0	0	None	0	None	0	0	0
T/I	rs367816473	0.193	0.002	D	0.349	0.16	None	gnomAD-3.1.2	1.71012E-04	None	None	None	None	N	None	5.31221E-04	1.96541E-04	0	0	0	None	0	0	0	0	4.79846E-04
T/I	rs367816473	0.193	0.002	D	0.349	0.16	None	gnomAD-4.0.0	2.78956E-05	None	None	None	None	N	None	4.54193E-04	8.34168E-05	None	0	0	None	0	0	8.47761E-07	0	8.00897E-05

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	0.0947	likely_benign	0.1019	benign	-0.937	Destabilizing	0.027	N	0.286	neutral	N	0.502416058	None	None	N
T/C	0.2784	likely_benign	0.3336	benign	-0.516	Destabilizing	0.824	D	0.536	neutral	None	None	None	None	N
T/D	0.4617	ambiguous	0.5301	ambiguous	-0.867	Destabilizing	0.081	N	0.457	neutral	None	None	None	None	N
T/E	0.3098	likely_benign	0.3504	ambiguous	-0.702	Destabilizing	0.081	N	0.454	neutral	None	None	None	None	N
T/F	0.1804	likely_benign	0.2257	benign	-0.538	Destabilizing	0.555	D	0.583	neutral	None	None	None	None	N
T/G	0.2482	likely_benign	0.2915	benign	-1.34	Destabilizing	0.081	N	0.504	neutral	None	None	None	None	N
T/H	0.2326	likely_benign	0.2585	benign	-1.468	Destabilizing	0.824	D	0.601	neutral	None	None	None	None	N
T/I	0.1278	likely_benign	0.1405	benign	0.105	Stabilizing	0.002	N	0.349	neutral	D	0.523023404	None	None	N
T/K	0.2567	likely_benign	0.2642	benign	-0.49	Destabilizing	0.081	N	0.461	neutral	None	None	None	None	N
T/L	0.0949	likely_benign	0.1031	benign	0.105	Stabilizing	0.035	N	0.439	neutral	None	None	None	None	N
T/M	0.0884	likely_benign	0.0859	benign	0.075	Stabilizing	0.555	D	0.538	neutral	None	None	None	None	N
T/N	0.1406	likely_benign	0.149	benign	-0.962	Destabilizing	0.062	N	0.415	neutral	N	0.512574337	None	None	N
T/P	0.7819	likely_pathogenic	0.7825	pathogenic	-0.21	Destabilizing	0.317	N	0.528	neutral	N	0.515632372	None	None	N
T/Q	0.2214	likely_benign	0.2299	benign	-0.783	Destabilizing	0.38	N	0.53	neutral	None	None	None	None	N
T/R	0.214	likely_benign	0.2258	benign	-0.656	Destabilizing	0.001	N	0.362	neutral	None	None	None	None	N
T/S	0.0955	likely_benign	0.1104	benign	-1.218	Destabilizing	None	N	0.202	neutral	N	0.40984704	None	None	N
T/V	0.1164	likely_benign	0.1238	benign	-0.21	Destabilizing	0.001	N	0.185	neutral	None	None	None	None	N
T/W	0.516	ambiguous	0.6031	pathogenic	-0.665	Destabilizing	0.935	D	0.638	neutral	None	None	None	None	N
T/Y	0.224	likely_benign	0.2744	benign	-0.308	Destabilizing	0.555	D	0.573	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.