TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30884	92875;92876;92877	chr2:178548976;178548975;178548974	chr2:179413703;179413702;179413701
N2AB	29243	87952;87953;87954	chr2:178548976;178548975;178548974	chr2:179413703;179413702;179413701
N2A	28316	85171;85172;85173	chr2:178548976;178548975;178548974	chr2:179413703;179413702;179413701
N2B	21819	65680;65681;65682	chr2:178548976;178548975;178548974	chr2:179413703;179413702;179413701
Novex-1	21944	66055;66056;66057	chr2:178548976;178548975;178548974	chr2:179413703;179413702;179413701
Novex-2	22011	66256;66257;66258	chr2:178548976;178548975;178548974	chr2:179413703;179413702;179413701
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: Fn3-113
• Domain position: 64
• Structural Position: 94
• Q(SASA): 0.3997
• 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	rs1698294296	None	0.891	N	0.448	0.282	0.314417295294	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
T/N	rs1698294296	None	0.891	N	0.448	0.282	0.314417295294	gnomAD-4.0.0	1.23933E-06	None	None	None	None	N	None	2.67023E-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	0.0785	likely_benign	0.0812	benign	-0.532	Destabilizing	0.454	N	0.391	neutral	D	0.526602427	None	None	N
T/C	0.3489	ambiguous	0.3969	ambiguous	-0.308	Destabilizing	0.998	D	0.542	neutral	None	None	None	None	N
T/D	0.3667	ambiguous	0.3755	ambiguous	0.102	Stabilizing	0.915	D	0.546	neutral	None	None	None	None	N
T/E	0.262	likely_benign	0.2658	benign	0.046	Stabilizing	0.842	D	0.465	neutral	None	None	None	None	N
T/F	0.2722	likely_benign	0.3099	benign	-0.903	Destabilizing	0.974	D	0.608	neutral	None	None	None	None	N
T/G	0.1787	likely_benign	0.1968	benign	-0.704	Destabilizing	0.915	D	0.527	neutral	None	None	None	None	N
T/H	0.2351	likely_benign	0.2597	benign	-0.997	Destabilizing	0.998	D	0.591	neutral	None	None	None	None	N
T/I	0.1513	likely_benign	0.1823	benign	-0.188	Destabilizing	0.669	D	0.463	neutral	N	0.489592079	None	None	N
T/K	0.1401	likely_benign	0.1445	benign	-0.484	Destabilizing	0.029	N	0.239	neutral	None	None	None	None	N
T/L	0.0935	likely_benign	0.1059	benign	-0.188	Destabilizing	0.525	D	0.432	neutral	None	None	None	None	N
T/M	0.0842	likely_benign	0.0906	benign	0.041	Stabilizing	0.974	D	0.557	neutral	None	None	None	None	N
T/N	0.1168	likely_benign	0.121	benign	-0.289	Destabilizing	0.891	D	0.448	neutral	N	0.477764794	None	None	N
T/P	0.0883	likely_benign	0.0853	benign	-0.272	Destabilizing	0.989	D	0.568	neutral	N	0.495279442	None	None	N
T/Q	0.1819	likely_benign	0.1913	benign	-0.507	Destabilizing	0.949	D	0.573	neutral	None	None	None	None	N
T/R	0.1402	likely_benign	0.1492	benign	-0.207	Destabilizing	0.728	D	0.511	neutral	None	None	None	None	N
T/S	0.103	likely_benign	0.1072	benign	-0.531	Destabilizing	0.801	D	0.418	neutral	N	0.46947692	None	None	N
T/V	0.1201	likely_benign	0.141	benign	-0.272	Destabilizing	0.007	N	0.159	neutral	None	None	None	None	N
T/W	0.5873	likely_pathogenic	0.6333	pathogenic	-0.871	Destabilizing	0.998	D	0.617	neutral	None	None	None	None	N
T/Y	0.3264	likely_benign	0.3599	ambiguous	-0.609	Destabilizing	0.991	D	0.612	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.