TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19496	58711;58712;58713	chr2:178593814;178593813;178593812	chr2:179458541;179458540;179458539
N2AB	17855	53788;53789;53790	chr2:178593814;178593813;178593812	chr2:179458541;179458540;179458539
N2A	16928	51007;51008;51009	chr2:178593814;178593813;178593812	chr2:179458541;179458540;179458539
N2B	10431	31516;31517;31518	chr2:178593814;178593813;178593812	chr2:179458541;179458540;179458539
Novex-1	10556	31891;31892;31893	chr2:178593814;178593813;178593812	chr2:179458541;179458540;179458539
Novex-2	10623	32092;32093;32094	chr2:178593814;178593813;178593812	chr2:179458541;179458540;179458539
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Fn3-29
• Domain position: 18
• Structural Position: 19
• Q(SASA): 0.4231
• 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
Y/F	None	None	None	N	0.131	0.126	0.293147016451	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
Y/S	None	None	0.117	N	0.513	0.253	0.442567846599	gnomAD-4.0.0	1.20032E-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
Y/A	0.219	likely_benign	0.2454	benign	-2.605	Highly Destabilizing	0.149	N	0.482	neutral	None	None	None	None	N
Y/C	0.0715	likely_benign	0.0846	benign	-0.974	Destabilizing	0.915	D	0.547	neutral	N	0.45799049	None	None	N
Y/D	0.1642	likely_benign	0.1919	benign	-1.644	Destabilizing	0.062	N	0.583	neutral	N	0.500490474	None	None	N
Y/E	0.3659	ambiguous	0.4198	ambiguous	-1.567	Destabilizing	0.081	N	0.523	neutral	None	None	None	None	N
Y/F	0.0724	likely_benign	0.0742	benign	-1.159	Destabilizing	None	N	0.131	neutral	N	0.445157266	None	None	N
Y/G	0.2229	likely_benign	0.2407	benign	-2.917	Highly Destabilizing	0.149	N	0.526	neutral	None	None	None	None	N
Y/H	0.0619	likely_benign	0.0764	benign	-1.325	Destabilizing	None	N	0.101	neutral	N	0.406465592	None	None	N
Y/I	0.3161	likely_benign	0.3445	ambiguous	-1.642	Destabilizing	0.38	N	0.573	neutral	None	None	None	None	N
Y/K	0.3815	ambiguous	0.4155	ambiguous	-1.383	Destabilizing	0.149	N	0.561	neutral	None	None	None	None	N
Y/L	0.336	likely_benign	0.3706	ambiguous	-1.642	Destabilizing	0.081	N	0.472	neutral	None	None	None	None	N
Y/M	0.4003	ambiguous	0.4423	ambiguous	-1.151	Destabilizing	0.791	D	0.538	neutral	None	None	None	None	N
Y/N	0.0607	likely_benign	0.0725	benign	-1.654	Destabilizing	0.002	N	0.368	neutral	N	0.434862915	None	None	N
Y/P	0.9695	likely_pathogenic	0.9728	pathogenic	-1.962	Destabilizing	0.555	D	0.582	neutral	None	None	None	None	N
Y/Q	0.219	likely_benign	0.2781	benign	-1.655	Destabilizing	0.38	N	0.597	neutral	None	None	None	None	N
Y/R	0.2281	likely_benign	0.2644	benign	-0.817	Destabilizing	0.38	N	0.594	neutral	None	None	None	None	N
Y/S	0.0642	likely_benign	0.0716	benign	-2.105	Highly Destabilizing	0.117	N	0.513	neutral	N	0.333671626	None	None	N
Y/T	0.1413	likely_benign	0.1595	benign	-1.942	Destabilizing	0.149	N	0.563	neutral	None	None	None	None	N
Y/V	0.241	likely_benign	0.2632	benign	-1.962	Destabilizing	0.149	N	0.512	neutral	None	None	None	None	N
Y/W	0.3932	ambiguous	0.4282	ambiguous	-0.725	Destabilizing	0.935	D	0.485	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.