TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33176	99751;99752;99753	chr2:178537681;178537680;178537679	chr2:179402408;179402407;179402406
N2AB	31535	94828;94829;94830	chr2:178537681;178537680;178537679	chr2:179402408;179402407;179402406
N2A	30608	92047;92048;92049	chr2:178537681;178537680;178537679	chr2:179402408;179402407;179402406
N2B	24111	72556;72557;72558	chr2:178537681;178537680;178537679	chr2:179402408;179402407;179402406
Novex-1	24236	72931;72932;72933	chr2:178537681;178537680;178537679	chr2:179402408;179402407;179402406
Novex-2	24303	73132;73133;73134	chr2:178537681;178537680;178537679	chr2:179402408;179402407;179402406
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-156
• Domain position: 76
• Structural Position: 159
• Q(SASA): 0.2429
• 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	None	None	0.005	N	0.165	0.187	0.486422812247	gnomAD-4.0.0	6.84222E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99465E-07	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	0.0747	likely_benign	0.083	benign	-0.809	Destabilizing	None	N	0.098	neutral	D	0.527827083	None	None	N
T/C	0.3244	likely_benign	0.3696	ambiguous	-0.71	Destabilizing	0.95	D	0.512	neutral	None	None	None	None	N
T/D	0.4281	ambiguous	0.5181	ambiguous	-1.253	Destabilizing	0.642	D	0.509	neutral	None	None	None	None	N
T/E	0.2789	likely_benign	0.3134	benign	-1.212	Destabilizing	0.457	N	0.517	neutral	None	None	None	None	N
T/F	0.2434	likely_benign	0.3222	benign	-0.736	Destabilizing	0.917	D	0.609	neutral	None	None	None	None	N
T/G	0.2256	likely_benign	0.2659	benign	-1.109	Destabilizing	0.514	D	0.601	neutral	None	None	None	None	N
T/H	0.2279	likely_benign	0.2565	benign	-1.43	Destabilizing	0.99	D	0.581	neutral	None	None	None	None	N
T/I	0.1184	likely_benign	0.1659	benign	-0.086	Destabilizing	0.005	N	0.165	neutral	N	0.511974983	None	None	N
T/K	0.1637	likely_benign	0.1678	benign	-1.019	Destabilizing	0.54	D	0.52	neutral	None	None	None	None	N
T/L	0.1006	likely_benign	0.1259	benign	-0.086	Destabilizing	0.002	N	0.171	neutral	None	None	None	None	N
T/M	0.0905	likely_benign	0.1089	benign	0.201	Stabilizing	0.805	D	0.523	neutral	None	None	None	None	N
T/N	0.1182	likely_benign	0.1452	benign	-1.194	Destabilizing	0.575	D	0.458	neutral	D	0.533638334	None	None	N
T/P	0.7253	likely_pathogenic	0.7693	pathogenic	-0.294	Destabilizing	0.575	D	0.513	neutral	D	0.532491265	None	None	N
T/Q	0.1797	likely_benign	0.192	benign	-1.331	Destabilizing	0.797	D	0.527	neutral	None	None	None	None	N
T/R	0.1332	likely_benign	0.1402	benign	-0.787	Destabilizing	0.957	D	0.525	neutral	None	None	None	None	N
T/S	0.0983	likely_benign	0.1046	benign	-1.325	Destabilizing	0.013	N	0.377	neutral	N	0.441650893	None	None	N
T/V	0.0994	likely_benign	0.123	benign	-0.294	Destabilizing	0.001	N	0.113	neutral	None	None	None	None	N
T/W	0.6155	likely_pathogenic	0.6885	pathogenic	-0.764	Destabilizing	0.996	D	0.608	neutral	None	None	None	None	N
T/Y	0.302	likely_benign	0.3731	ambiguous	-0.496	Destabilizing	0.957	D	0.619	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.