TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18046	54361;54362;54363	chr2:178605041;178605040;178605039	chr2:179469768;179469767;179469766
N2AB	16405	49438;49439;49440	chr2:178605041;178605040;178605039	chr2:179469768;179469767;179469766
N2A	15478	46657;46658;46659	chr2:178605041;178605040;178605039	chr2:179469768;179469767;179469766
N2B	8981	27166;27167;27168	chr2:178605041;178605040;178605039	chr2:179469768;179469767;179469766
Novex-1	9106	27541;27542;27543	chr2:178605041;178605040;178605039	chr2:179469768;179469767;179469766
Novex-2	9173	27742;27743;27744	chr2:178605041;178605040;178605039	chr2:179469768;179469767;179469766
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-114
• Domain position: 79
• Structural Position: 157
• Q(SASA): 0.1875
• 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/N	None	None	0.934	D	0.558	0.251	0.485991781493	gnomAD-4.0.0	1.3714E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.3271E-05	0
T/S	None	None	0.136	N	0.407	0.184	0.212008924253	gnomAD-4.0.0	2.05709E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80216E-06	1.16355E-05	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	0.1141	likely_benign	0.1209	benign	-1.124	Destabilizing	0.454	N	0.482	neutral	N	0.497253353	None	None	N
T/C	0.4098	ambiguous	0.4426	ambiguous	-0.918	Destabilizing	0.081	N	0.46	neutral	None	None	None	None	N
T/D	0.7216	likely_pathogenic	0.7318	pathogenic	-1.058	Destabilizing	0.949	D	0.581	neutral	None	None	None	None	N
T/E	0.4437	ambiguous	0.4857	ambiguous	-0.969	Destabilizing	0.842	D	0.57	neutral	None	None	None	None	N
T/F	0.2673	likely_benign	0.2965	benign	-1.046	Destabilizing	0.949	D	0.669	neutral	None	None	None	None	N
T/G	0.3995	ambiguous	0.4093	ambiguous	-1.441	Destabilizing	0.842	D	0.623	neutral	None	None	None	None	N
T/H	0.2407	likely_benign	0.2838	benign	-1.679	Destabilizing	0.993	D	0.662	neutral	None	None	None	None	N
T/I	0.1751	likely_benign	0.1925	benign	-0.34	Destabilizing	0.669	D	0.573	neutral	N	0.488711334	None	None	N
T/K	0.179	likely_benign	0.2255	benign	-0.696	Destabilizing	0.728	D	0.541	neutral	None	None	None	None	N
T/L	0.115	likely_benign	0.1234	benign	-0.34	Destabilizing	0.016	N	0.393	neutral	None	None	None	None	N
T/M	0.0887	likely_benign	0.0901	benign	-0.193	Destabilizing	0.949	D	0.581	neutral	None	None	None	None	N
T/N	0.2144	likely_benign	0.2122	benign	-0.962	Destabilizing	0.934	D	0.558	neutral	D	0.53217411	None	None	N
T/P	0.9024	likely_pathogenic	0.9092	pathogenic	-0.571	Destabilizing	0.966	D	0.602	neutral	D	0.525272336	None	None	N
T/Q	0.2318	likely_benign	0.2571	benign	-1.047	Destabilizing	0.949	D	0.596	neutral	None	None	None	None	N
T/R	0.1585	likely_benign	0.2047	benign	-0.627	Destabilizing	0.037	N	0.403	neutral	None	None	None	None	N
T/S	0.1582	likely_benign	0.1538	benign	-1.216	Destabilizing	0.136	N	0.407	neutral	N	0.502640637	None	None	N
T/V	0.1366	likely_benign	0.1482	benign	-0.571	Destabilizing	0.728	D	0.551	neutral	None	None	None	None	N
T/W	0.5949	likely_pathogenic	0.6497	pathogenic	-1.025	Destabilizing	0.998	D	0.696	prob.neutral	None	None	None	None	N
T/Y	0.2936	likely_benign	0.334	benign	-0.724	Destabilizing	0.991	D	0.661	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.