TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23497	70714;70715;70716	chr2:178575643;178575642;178575641	chr2:179440370;179440369;179440368
N2AB	21856	65791;65792;65793	chr2:178575643;178575642;178575641	chr2:179440370;179440369;179440368
N2A	20929	63010;63011;63012	chr2:178575643;178575642;178575641	chr2:179440370;179440369;179440368
N2B	14432	43519;43520;43521	chr2:178575643;178575642;178575641	chr2:179440370;179440369;179440368
Novex-1	14557	43894;43895;43896	chr2:178575643;178575642;178575641	chr2:179440370;179440369;179440368
Novex-2	14624	44095;44096;44097	chr2:178575643;178575642;178575641	chr2:179440370;179440369;179440368
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: Fn3-58
• Domain position: 63
• Structural Position: 94
• Q(SASA): 0.493
• 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	0.966	N	0.575	0.351	0.409665357357	gnomAD-4.0.0	1.5917E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85915E-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
T/A	0.07	likely_benign	0.0698	benign	-0.673	Destabilizing	0.454	N	0.367	neutral	N	0.476145406	None	None	N
T/C	0.3045	likely_benign	0.3079	benign	-0.387	Destabilizing	0.998	D	0.545	neutral	None	None	None	None	N
T/D	0.267	likely_benign	0.2682	benign	0.146	Stabilizing	0.842	D	0.486	neutral	None	None	None	None	N
T/E	0.2242	likely_benign	0.2265	benign	0.104	Stabilizing	0.842	D	0.463	neutral	None	None	None	None	N
T/F	0.1826	likely_benign	0.1918	benign	-0.981	Destabilizing	0.991	D	0.624	neutral	None	None	None	None	N
T/G	0.1502	likely_benign	0.1472	benign	-0.864	Destabilizing	0.842	D	0.522	neutral	None	None	None	None	N
T/H	0.1988	likely_benign	0.1934	benign	-1.104	Destabilizing	0.998	D	0.61	neutral	None	None	None	None	N
T/I	0.1144	likely_benign	0.1221	benign	-0.276	Destabilizing	0.966	D	0.575	neutral	N	0.488933743	None	None	N
T/K	0.1999	likely_benign	0.193	benign	-0.545	Destabilizing	0.842	D	0.475	neutral	None	None	None	None	N
T/L	0.0738	likely_benign	0.0753	benign	-0.276	Destabilizing	0.842	D	0.469	neutral	None	None	None	None	N
T/M	0.0799	likely_benign	0.0765	benign	-0.016	Destabilizing	0.998	D	0.551	neutral	None	None	None	None	N
T/N	0.0937	likely_benign	0.092	benign	-0.379	Destabilizing	0.801	D	0.433	neutral	N	0.468548082	None	None	N
T/P	0.0754	likely_benign	0.0778	benign	-0.378	Destabilizing	0.002	N	0.241	neutral	N	0.50524572	None	None	N
T/Q	0.1885	likely_benign	0.1786	benign	-0.579	Destabilizing	0.974	D	0.576	neutral	None	None	None	None	N
T/R	0.1904	likely_benign	0.1895	benign	-0.263	Destabilizing	0.974	D	0.579	neutral	None	None	None	None	N
T/S	0.0803	likely_benign	0.0776	benign	-0.669	Destabilizing	0.136	N	0.216	neutral	N	0.450083083	None	None	N
T/V	0.098	likely_benign	0.1012	benign	-0.378	Destabilizing	0.915	D	0.377	neutral	None	None	None	None	N
T/W	0.4871	ambiguous	0.4907	ambiguous	-0.92	Destabilizing	0.998	D	0.656	neutral	None	None	None	None	N
T/Y	0.2307	likely_benign	0.2393	benign	-0.676	Destabilizing	0.991	D	0.627	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.