TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3157	9694;9695;9696	chr2:178767761;178767760;178767759	chr2:179632488;179632487;179632486
N2AB	3157	9694;9695;9696	chr2:178767761;178767760;178767759	chr2:179632488;179632487;179632486
N2A	3157	9694;9695;9696	chr2:178767761;178767760;178767759	chr2:179632488;179632487;179632486
N2B	3111	9556;9557;9558	chr2:178767761;178767760;178767759	chr2:179632488;179632487;179632486
Novex-1	3111	9556;9557;9558	chr2:178767761;178767760;178767759	chr2:179632488;179632487;179632486
Novex-2	3111	9556;9557;9558	chr2:178767761;178767760;178767759	chr2:179632488;179632487;179632486
Novex-3	3157	9694;9695;9696	chr2:178767761;178767760;178767759	chr2:179632488;179632487;179632486

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-22
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.8128
• 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
Q/R	None	None	0.801	N	0.342	0.213	0.265929055128	gnomAD-4.0.0	2.05251E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79862E-06	1.15934E-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
Q/A	0.245	likely_benign	0.2987	benign	-0.427	Destabilizing	0.325	N	0.343	neutral	None	None	None	None	N
Q/C	0.771	likely_pathogenic	0.8487	pathogenic	0.058	Stabilizing	0.998	D	0.351	neutral	None	None	None	None	N
Q/D	0.443	ambiguous	0.5572	ambiguous	0.253	Stabilizing	0.525	D	0.321	neutral	None	None	None	None	N
Q/E	0.0805	likely_benign	0.1037	benign	0.3	Stabilizing	0.005	N	0.123	neutral	N	0.436750209	None	None	N
Q/F	0.7808	likely_pathogenic	0.827	pathogenic	-0.312	Destabilizing	0.991	D	0.384	neutral	None	None	None	None	N
Q/G	0.449	ambiguous	0.5581	ambiguous	-0.707	Destabilizing	0.688	D	0.339	neutral	None	None	None	None	N
Q/H	0.256	likely_benign	0.2969	benign	-0.403	Destabilizing	0.966	D	0.391	neutral	N	0.499531806	None	None	N
Q/I	0.4855	ambiguous	0.5544	ambiguous	0.25	Stabilizing	0.949	D	0.417	neutral	None	None	None	None	N
Q/K	0.1115	likely_benign	0.1793	benign	0.023	Stabilizing	0.454	N	0.367	neutral	N	0.457877147	None	None	N
Q/L	0.1881	likely_benign	0.2358	benign	0.25	Stabilizing	0.801	D	0.381	neutral	N	0.510879594	None	None	N
Q/M	0.4204	ambiguous	0.4872	ambiguous	0.419	Stabilizing	0.991	D	0.396	neutral	None	None	None	None	N
Q/N	0.3325	likely_benign	0.3505	ambiguous	-0.474	Destabilizing	0.842	D	0.297	neutral	None	None	None	None	N
Q/P	0.2367	likely_benign	0.3219	benign	0.055	Stabilizing	0.891	D	0.433	neutral	N	0.512649789	None	None	N
Q/R	0.138	likely_benign	0.2021	benign	0.127	Stabilizing	0.801	D	0.342	neutral	N	0.49795071	None	None	N
Q/S	0.3091	likely_benign	0.3257	benign	-0.569	Destabilizing	0.08	N	0.12	neutral	None	None	None	None	N
Q/T	0.2095	likely_benign	0.2468	benign	-0.332	Destabilizing	0.029	N	0.151	neutral	None	None	None	None	N
Q/V	0.3166	likely_benign	0.3714	ambiguous	0.055	Stabilizing	0.842	D	0.403	neutral	None	None	None	None	N
Q/W	0.6791	likely_pathogenic	0.7887	pathogenic	-0.203	Destabilizing	0.998	D	0.362	neutral	None	None	None	None	N
Q/Y	0.5903	likely_pathogenic	0.6566	pathogenic	0.024	Stabilizing	0.991	D	0.39	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.