TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16120	48583;48584;48585	chr2:178615743;178615742;178615741	chr2:179480470;179480469;179480468
N2AB	14479	43660;43661;43662	chr2:178615743;178615742;178615741	chr2:179480470;179480469;179480468
N2A	13552	40879;40880;40881	chr2:178615743;178615742;178615741	chr2:179480470;179480469;179480468
N2B	7055	21388;21389;21390	chr2:178615743;178615742;178615741	chr2:179480470;179480469;179480468
Novex-1	7180	21763;21764;21765	chr2:178615743;178615742;178615741	chr2:179480470;179480469;179480468
Novex-2	7247	21964;21965;21966	chr2:178615743;178615742;178615741	chr2:179480470;179480469;179480468
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-4
• Domain position: 66
• Structural Position: 98
• Q(SASA): 0.3681
• 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
V/A	rs745999025	-1.528	None	N	0.091	0.135	0.330069100803	gnomAD-2.1.1	7.16E-06	None	None	None	None	N	None	8.28E-05	0	None	0	0	None	0	None	0	0	0
V/A	rs745999025	-1.528	None	N	0.091	0.135	0.330069100803	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	9.66E-05	0	0	0	0	None	0	0	0	0	0
V/A	rs745999025	-1.528	None	N	0.091	0.135	0.330069100803	gnomAD-4.0.0	5.07592E-06	None	None	None	None	N	None	6.99423E-05	0	None	0	0	None	0	0	1.20507E-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
V/A	0.2043	likely_benign	0.2482	benign	-1.181	Destabilizing	None	N	0.091	neutral	N	0.479377875	None	None	N
V/C	0.61	likely_pathogenic	0.6975	pathogenic	-0.812	Destabilizing	0.824	D	0.357	neutral	None	None	None	None	N
V/D	0.4733	ambiguous	0.5322	ambiguous	-0.901	Destabilizing	0.484	N	0.419	neutral	N	0.480707155	None	None	N
V/E	0.3288	likely_benign	0.3882	ambiguous	-0.914	Destabilizing	0.38	N	0.392	neutral	None	None	None	None	N
V/F	0.1602	likely_benign	0.1938	benign	-0.928	Destabilizing	0.188	N	0.372	neutral	N	0.480559353	None	None	N
V/G	0.234	likely_benign	0.2716	benign	-1.464	Destabilizing	0.062	N	0.371	neutral	D	0.61158625	None	None	N
V/H	0.4758	ambiguous	0.5764	pathogenic	-0.862	Destabilizing	0.935	D	0.402	neutral	None	None	None	None	N
V/I	0.0678	likely_benign	0.0743	benign	-0.521	Destabilizing	None	N	0.082	neutral	N	0.413362327	None	None	N
V/K	0.3634	ambiguous	0.4512	ambiguous	-0.963	Destabilizing	0.38	N	0.386	neutral	None	None	None	None	N
V/L	0.1017	likely_benign	0.1445	benign	-0.521	Destabilizing	None	N	0.068	neutral	N	0.466984545	None	None	N
V/M	0.1206	likely_benign	0.1525	benign	-0.488	Destabilizing	0.016	N	0.223	neutral	None	None	None	None	N
V/N	0.265	likely_benign	0.3311	benign	-0.778	Destabilizing	0.555	D	0.423	neutral	None	None	None	None	N
V/P	0.4723	ambiguous	0.5316	ambiguous	-0.705	Destabilizing	0.555	D	0.407	neutral	None	None	None	None	N
V/Q	0.2395	likely_benign	0.3158	benign	-0.942	Destabilizing	0.555	D	0.407	neutral	None	None	None	None	N
V/R	0.3342	likely_benign	0.4137	ambiguous	-0.424	Destabilizing	0.555	D	0.427	neutral	None	None	None	None	N
V/S	0.216	likely_benign	0.2581	benign	-1.263	Destabilizing	0.081	N	0.39	neutral	None	None	None	None	N
V/T	0.1957	likely_benign	0.2379	benign	-1.161	Destabilizing	0.149	N	0.223	neutral	None	None	None	None	N
V/W	0.7258	likely_pathogenic	0.8083	pathogenic	-1.077	Destabilizing	0.935	D	0.444	neutral	None	None	None	None	N
V/Y	0.4856	ambiguous	0.5677	pathogenic	-0.781	Destabilizing	0.555	D	0.373	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.