TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15850	47773;47774;47775	chr2:178617803;178617802;178617801	chr2:179482530;179482529;179482528
N2AB	14209	42850;42851;42852	chr2:178617803;178617802;178617801	chr2:179482530;179482529;179482528
N2A	13282	40069;40070;40071	chr2:178617803;178617802;178617801	chr2:179482530;179482529;179482528
N2B	6785	20578;20579;20580	chr2:178617803;178617802;178617801	chr2:179482530;179482529;179482528
Novex-1	6910	20953;20954;20955	chr2:178617803;178617802;178617801	chr2:179482530;179482529;179482528
Novex-2	6977	21154;21155;21156	chr2:178617803;178617802;178617801	chr2:179482530;179482529;179482528
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Fn3-2
• Domain position: 93
• Structural Position: 127
• Q(SASA): 0.43
• 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
F/C	rs1462059025	-0.461	0.855	N	0.502	0.31	0.470237251169	gnomAD-2.1.1	5.65E-05	None	None	None	None	I	None	0	3.77995E-04	None	0	0	None	0	None	0	0	1.66168E-04
F/C	rs1462059025	-0.461	0.855	N	0.502	0.31	0.470237251169	gnomAD-3.1.2	1.31662E-04	None	None	None	None	I	None	0	1.24803E-03	0	0	0	None	0	0	0	0	4.78927E-04
F/C	rs1462059025	-0.461	0.855	N	0.502	0.31	0.470237251169	gnomAD-4.0.0	4.36394E-05	None	None	None	None	I	None	0	5.60386E-04	None	0	0	None	0	0	0	0	2.85144E-05
F/L	rs113350914	None	0.255	N	0.242	0.179	0.104622674875	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	4.64E-05	0	0
F/L	rs113350914	None	0.255	N	0.242	0.179	0.104622674875	gnomAD-4.0.0	2.73929E-06	None	None	None	None	I	None	8.98957E-05	0	None	0	0	None	0	0	0	0	1.65904E-05
F/S	rs1462059025	-1.153	0.146	N	0.282	0.251	0.436025050644	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	1.14784E-04	0	None	0	0	None	0	None	0	0	0
F/S	rs1462059025	-1.153	0.146	N	0.282	0.251	0.436025050644	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
F/S	rs1462059025	-1.153	0.146	N	0.282	0.251	0.436025050644	gnomAD-4.0.0	3.85054E-06	None	None	None	None	I	None	5.08337E-05	0	None	0	0	None	0	0	0	0	0
F/V	rs1183898794	-0.805	0.146	N	0.254	0.147	0.394685799254	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	5.62E-05	None	0	None	0	0	0
F/V	rs1183898794	-0.805	0.146	N	0.254	0.147	0.394685799254	gnomAD-4.0.0	1.5944E-06	None	None	None	None	I	None	0	0	None	0	2.78365E-05	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
F/A	0.32	likely_benign	0.2437	benign	-2.274	Highly Destabilizing	None	N	0.221	neutral	None	None	None	None	I
F/C	0.2684	likely_benign	0.2414	benign	-1.03	Destabilizing	0.855	D	0.502	neutral	N	0.464347269	None	None	I
F/D	0.7562	likely_pathogenic	0.6957	pathogenic	-0.79	Destabilizing	0.691	D	0.439	neutral	None	None	None	None	I
F/E	0.8061	likely_pathogenic	0.7556	pathogenic	-0.719	Destabilizing	0.312	N	0.388	neutral	None	None	None	None	I
F/G	0.6567	likely_pathogenic	0.5868	pathogenic	-2.588	Highly Destabilizing	0.185	N	0.25	neutral	None	None	None	None	I
F/H	0.4977	ambiguous	0.4433	ambiguous	-0.742	Destabilizing	0.96	D	0.419	neutral	None	None	None	None	I
F/I	0.2434	likely_benign	0.2115	benign	-1.337	Destabilizing	0.454	N	0.205	neutral	N	0.415199824	None	None	I
F/K	0.8352	likely_pathogenic	0.7787	pathogenic	-1.038	Destabilizing	0.524	D	0.428	neutral	None	None	None	None	I
F/L	0.7353	likely_pathogenic	0.6702	pathogenic	-1.337	Destabilizing	0.255	N	0.242	neutral	N	0.378756448	None	None	I
F/M	0.4439	ambiguous	0.3884	ambiguous	-0.981	Destabilizing	0.96	D	0.413	neutral	None	None	None	None	I
F/N	0.4953	ambiguous	0.4309	ambiguous	-0.992	Destabilizing	0.691	D	0.609	neutral	None	None	None	None	I
F/P	0.6652	likely_pathogenic	0.5641	pathogenic	-1.642	Destabilizing	None	N	0.257	neutral	None	None	None	None	I
F/Q	0.7139	likely_pathogenic	0.6522	pathogenic	-1.143	Destabilizing	0.887	D	0.618	neutral	None	None	None	None	I
F/R	0.708	likely_pathogenic	0.6399	pathogenic	-0.307	Destabilizing	0.691	D	0.59	neutral	None	None	None	None	I
F/S	0.2823	likely_benign	0.228	benign	-1.839	Destabilizing	0.146	N	0.282	neutral	N	0.397981787	None	None	I
F/T	0.402	ambiguous	0.3225	benign	-1.685	Destabilizing	0.312	N	0.321	neutral	None	None	None	None	I
F/V	0.205	likely_benign	0.1709	benign	-1.642	Destabilizing	0.146	N	0.254	neutral	N	0.407936242	None	None	I
F/W	0.4779	ambiguous	0.4375	ambiguous	-0.374	Destabilizing	0.989	D	0.469	neutral	None	None	None	None	I
F/Y	0.1353	likely_benign	0.1243	benign	-0.58	Destabilizing	0.837	D	0.294	neutral	N	0.43437941	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.