TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31372	94339;94340;94341	chr2:178547512;178547511;178547510	chr2:179412239;179412238;179412237
N2AB	29731	89416;89417;89418	chr2:178547512;178547511;178547510	chr2:179412239;179412238;179412237
N2A	28804	86635;86636;86637	chr2:178547512;178547511;178547510	chr2:179412239;179412238;179412237
N2B	22307	67144;67145;67146	chr2:178547512;178547511;178547510	chr2:179412239;179412238;179412237
Novex-1	22432	67519;67520;67521	chr2:178547512;178547511;178547510	chr2:179412239;179412238;179412237
Novex-2	22499	67720;67721;67722	chr2:178547512;178547511;178547510	chr2:179412239;179412238;179412237
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-116
• Domain position: 65
• Structural Position: 96
• Q(SASA): 0.9501
• Predicted PPI site: I

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
H/L	rs761630773	0.729	0.968	N	0.521	0.319	0.347659731818	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
H/L	rs761630773	0.729	0.968	N	0.521	0.319	0.347659731818	gnomAD-4.0.0	2.0529E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79899E-06	0	1.65689E-05
H/R	rs761630773	-0.054	0.026	N	0.279	0.176	0.168933306366	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	0	8.71E-05	None	0	0	None	0	None	0	0	0
H/R	rs761630773	-0.054	0.026	N	0.279	0.176	0.168933306366	gnomAD-3.1.2	3.94E-05	None	None	None	None	I	None	0	3.92876E-04	0	0	0	None	0	0	0	0	0
H/R	rs761630773	-0.054	0.026	N	0.279	0.176	0.168933306366	gnomAD-4.0.0	6.19749E-06	None	None	None	None	I	None	0	1.50055E-04	None	0	0	None	0	0	8.47629E-07	0	0
H/Y	rs1349108221	None	0.982	N	0.482	0.407	0.279776271856	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
H/Y	rs1349108221	None	0.982	N	0.482	0.407	0.279776271856	gnomAD-4.0.0	2.56291E-06	None	None	None	None	I	None	1.69165E-05	0	None	0	0	None	0	0	2.39329E-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
H/A	0.5219	ambiguous	0.4656	ambiguous	0.468	Stabilizing	0.919	D	0.452	neutral	None	None	None	None	I
H/C	0.3036	likely_benign	0.2789	benign	0.658	Stabilizing	0.999	D	0.641	neutral	None	None	None	None	I
H/D	0.4781	ambiguous	0.4244	ambiguous	-0.095	Destabilizing	0.984	D	0.455	neutral	N	0.386063316	None	None	I
H/E	0.6706	likely_pathogenic	0.621	pathogenic	-0.093	Destabilizing	0.919	D	0.463	neutral	None	None	None	None	I
H/F	0.5519	ambiguous	0.5349	ambiguous	0.965	Stabilizing	0.996	D	0.488	neutral	None	None	None	None	I
H/G	0.3784	ambiguous	0.3277	benign	0.244	Stabilizing	0.959	D	0.461	neutral	None	None	None	None	I
H/I	0.7666	likely_pathogenic	0.7377	pathogenic	1.015	Stabilizing	0.988	D	0.602	neutral	None	None	None	None	I
H/K	0.4185	ambiguous	0.3778	ambiguous	0.402	Stabilizing	0.851	D	0.455	neutral	None	None	None	None	I
H/L	0.3188	likely_benign	0.2866	benign	1.015	Stabilizing	0.968	D	0.521	neutral	N	0.466805973	None	None	I
H/M	0.7328	likely_pathogenic	0.693	pathogenic	0.704	Stabilizing	0.999	D	0.547	neutral	None	None	None	None	I
H/N	0.1348	likely_benign	0.1165	benign	0.322	Stabilizing	0.896	D	0.498	neutral	N	0.395413518	None	None	I
H/P	0.524	ambiguous	0.5127	ambiguous	0.856	Stabilizing	0.995	D	0.555	neutral	N	0.492790923	None	None	I
H/Q	0.3722	ambiguous	0.3066	benign	0.373	Stabilizing	0.968	D	0.511	neutral	N	0.477533469	None	None	I
H/R	0.1804	likely_benign	0.1583	benign	-0.071	Destabilizing	0.026	N	0.279	neutral	N	0.400054121	None	None	I
H/S	0.3677	ambiguous	0.3238	benign	0.434	Stabilizing	0.919	D	0.479	neutral	None	None	None	None	I
H/T	0.54	ambiguous	0.4856	ambiguous	0.529	Stabilizing	0.988	D	0.467	neutral	None	None	None	None	I
H/V	0.6456	likely_pathogenic	0.6024	pathogenic	0.856	Stabilizing	0.988	D	0.589	neutral	None	None	None	None	I
H/W	0.6358	likely_pathogenic	0.5993	pathogenic	0.86	Stabilizing	0.999	D	0.635	neutral	None	None	None	None	I
H/Y	0.1846	likely_benign	0.1763	benign	1.146	Stabilizing	0.982	D	0.482	neutral	N	0.512166118	None	None	I

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.