TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30198	90817;90818;90819	chr2:178552308;178552307;178552306	chr2:179417035;179417034;179417033
N2AB	28557	85894;85895;85896	chr2:178552308;178552307;178552306	chr2:179417035;179417034;179417033
N2A	27630	83113;83114;83115	chr2:178552308;178552307;178552306	chr2:179417035;179417034;179417033
N2B	21133	63622;63623;63624	chr2:178552308;178552307;178552306	chr2:179417035;179417034;179417033
Novex-1	21258	63997;63998;63999	chr2:178552308;178552307;178552306	chr2:179417035;179417034;179417033
Novex-2	21325	64198;64199;64200	chr2:178552308;178552307;178552306	chr2:179417035;179417034;179417033
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: Ig-148
• Domain position: 67
• Structural Position: 149
• Q(SASA): 0.2696
• 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
H/D	rs750619537	-0.789	None	N	0.399	0.124	0.0666544352282	gnomAD-2.1.1	8.11E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.79E-05	0
H/D	rs750619537	-0.789	None	N	0.399	0.124	0.0666544352282	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
H/D	rs750619537	-0.789	None	N	0.399	0.124	0.0666544352282	gnomAD-4.0.0	2.4814E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.3922E-06	0	0
H/Q	rs765307374	-0.568	0.001	N	0.354	0.111	0.242825505644	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
H/Q	rs765307374	-0.568	0.001	N	0.354	0.111	0.242825505644	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	4.41E-05	0	0
H/Q	rs765307374	-0.568	0.001	N	0.354	0.111	0.242825505644	gnomAD-4.0.0	1.24051E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.69597E-05	0	0
H/R	rs1479999162	-0.885	0.029	D	0.481	0.267	0.331619326243	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
H/R	rs1479999162	-0.885	0.029	D	0.481	0.267	0.331619326243	gnomAD-4.0.0	4.10941E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39956E-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	0.5149	ambiguous	0.3978	ambiguous	-1.28	Destabilizing	0.016	N	0.582	neutral	None	None	None	None	N
H/C	0.3247	likely_benign	0.2584	benign	-0.442	Destabilizing	0.864	D	0.745	deleterious	None	None	None	None	N
H/D	0.1602	likely_benign	0.1456	benign	-1.112	Destabilizing	None	N	0.399	neutral	N	0.350329016	None	None	N
H/E	0.591	likely_pathogenic	0.5312	ambiguous	-0.951	Destabilizing	0.007	N	0.453	neutral	None	None	None	None	N
H/F	0.4674	ambiguous	0.3707	ambiguous	0.393	Stabilizing	0.038	N	0.643	neutral	None	None	None	None	N
H/G	0.6402	likely_pathogenic	0.5646	pathogenic	-1.71	Destabilizing	0.016	N	0.57	neutral	None	None	None	None	N
H/I	0.6116	likely_pathogenic	0.4417	ambiguous	-0.044	Destabilizing	0.072	N	0.73	prob.delet.	None	None	None	None	N
H/K	0.7988	likely_pathogenic	0.7322	pathogenic	-0.846	Destabilizing	0.016	N	0.543	neutral	None	None	None	None	N
H/L	0.3193	likely_benign	0.2436	benign	-0.044	Destabilizing	0.029	N	0.653	neutral	N	0.500999108	None	None	N
H/M	0.5438	ambiguous	0.4239	ambiguous	-0.246	Destabilizing	0.356	N	0.733	prob.delet.	None	None	None	None	N
H/N	0.0543	likely_benign	0.0401	benign	-1.298	Destabilizing	None	N	0.282	neutral	N	0.482089219	None	None	N
H/P	0.825	likely_pathogenic	0.7621	pathogenic	-0.44	Destabilizing	0.106	N	0.685	prob.neutral	N	0.500745618	None	None	N
H/Q	0.3861	ambiguous	0.3408	ambiguous	-0.957	Destabilizing	0.001	N	0.354	neutral	N	0.48322537	None	None	N
H/R	0.6953	likely_pathogenic	0.6254	pathogenic	-1.334	Destabilizing	0.029	N	0.481	neutral	D	0.523783913	None	None	N
H/S	0.2983	likely_benign	0.2163	benign	-1.356	Destabilizing	0.016	N	0.517	neutral	None	None	None	None	N
H/T	0.4494	ambiguous	0.3163	benign	-1.068	Destabilizing	0.016	N	0.607	neutral	None	None	None	None	N
H/V	0.581	likely_pathogenic	0.4238	ambiguous	-0.44	Destabilizing	0.072	N	0.69	prob.neutral	None	None	None	None	N
H/W	0.7028	likely_pathogenic	0.6372	pathogenic	0.891	Stabilizing	0.676	D	0.725	prob.delet.	None	None	None	None	N
H/Y	0.156	likely_benign	0.1217	benign	0.785	Stabilizing	None	N	0.321	neutral	N	0.482641363	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.