TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29096	87511;87512;87513	chr2:178558068;178558067;178558066	chr2:179422795;179422794;179422793
N2AB	27455	82588;82589;82590	chr2:178558068;178558067;178558066	chr2:179422795;179422794;179422793
N2A	26528	79807;79808;79809	chr2:178558068;178558067;178558066	chr2:179422795;179422794;179422793
N2B	20031	60316;60317;60318	chr2:178558068;178558067;178558066	chr2:179422795;179422794;179422793
Novex-1	20156	60691;60692;60693	chr2:178558068;178558067;178558066	chr2:179422795;179422794;179422793
Novex-2	20223	60892;60893;60894	chr2:178558068;178558067;178558066	chr2:179422795;179422794;179422793
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: Ig-145
• Domain position: 52
• Structural Position: 130
• Q(SASA): 0.6322
• 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/A	rs1575589104	None	0.999	N	0.436	0.29	0.352048277211	gnomAD-4.0.0	1.59105E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85785E-06	0	0
T/I	None	None	1.0	D	0.655	0.474	0.657668229798	gnomAD-4.0.0	1.59105E-06	None	None	None	None	N	None	5.65163E-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
T/A	0.124	likely_benign	0.1111	benign	-0.443	Destabilizing	0.999	D	0.436	neutral	N	0.520418321	None	None	N
T/C	0.5015	ambiguous	0.4715	ambiguous	-0.291	Destabilizing	1.0	D	0.631	neutral	None	None	None	None	N
T/D	0.3658	ambiguous	0.331	benign	0.198	Stabilizing	1.0	D	0.664	neutral	None	None	None	None	N
T/E	0.4894	ambiguous	0.4369	ambiguous	0.135	Stabilizing	1.0	D	0.673	neutral	None	None	None	None	N
T/F	0.3646	ambiguous	0.3233	benign	-0.856	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
T/G	0.2016	likely_benign	0.1976	benign	-0.6	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
T/H	0.3179	likely_benign	0.2804	benign	-0.896	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
T/I	0.3737	ambiguous	0.3247	benign	-0.144	Destabilizing	1.0	D	0.655	neutral	D	0.52882716	None	None	N
T/K	0.3114	likely_benign	0.2719	benign	-0.418	Destabilizing	1.0	D	0.672	neutral	None	None	None	None	N
T/L	0.1538	likely_benign	0.1407	benign	-0.144	Destabilizing	0.999	D	0.561	neutral	None	None	None	None	N
T/M	0.1263	likely_benign	0.1171	benign	0.052	Stabilizing	1.0	D	0.634	neutral	None	None	None	None	N
T/N	0.1159	likely_benign	0.1146	benign	-0.23	Destabilizing	1.0	D	0.663	neutral	N	0.492519643	None	None	N
T/P	0.5013	ambiguous	0.411	ambiguous	-0.214	Destabilizing	1.0	D	0.649	neutral	D	0.52882716	None	None	N
T/Q	0.3306	likely_benign	0.3014	benign	-0.445	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
T/R	0.2813	likely_benign	0.2374	benign	-0.153	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	N
T/S	0.0892	likely_benign	0.0905	benign	-0.47	Destabilizing	0.999	D	0.458	neutral	N	0.473760524	None	None	N
T/V	0.2735	likely_benign	0.2404	benign	-0.214	Destabilizing	0.999	D	0.515	neutral	None	None	None	None	N
T/W	0.7215	likely_pathogenic	0.6741	pathogenic	-0.839	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
T/Y	0.4358	ambiguous	0.3975	ambiguous	-0.567	Destabilizing	1.0	D	0.689	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.