TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33541	100846;100847;100848	chr2:178536126;178536125;178536124	chr2:179400853;179400852;179400851
N2AB	31900	95923;95924;95925	chr2:178536126;178536125;178536124	chr2:179400853;179400852;179400851
N2A	30973	93142;93143;93144	chr2:178536126;178536125;178536124	chr2:179400853;179400852;179400851
N2B	24476	73651;73652;73653	chr2:178536126;178536125;178536124	chr2:179400853;179400852;179400851
Novex-1	24601	74026;74027;74028	chr2:178536126;178536125;178536124	chr2:179400853;179400852;179400851
Novex-2	24668	74227;74228;74229	chr2:178536126;178536125;178536124	chr2:179400853;179400852;179400851
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-158
• Domain position: 46
• Structural Position: 111
• Q(SASA): 0.7039
• 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
L/S	rs1283891499	-0.221	0.009	N	0.128	0.245	0.68565156927	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
L/S	rs1283891499	-0.221	0.009	N	0.128	0.245	0.68565156927	gnomAD-4.0.0	1.59168E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85884E-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
L/A	0.1062	likely_benign	0.1295	benign	-0.417	Destabilizing	0.059	N	0.187	neutral	None	None	None	None	I
L/C	0.3984	ambiguous	0.4379	ambiguous	-0.678	Destabilizing	0.983	D	0.181	neutral	None	None	None	None	I
L/D	0.3285	likely_benign	0.3417	ambiguous	-0.126	Destabilizing	0.126	N	0.227	neutral	None	None	None	None	I
L/E	0.1546	likely_benign	0.1573	benign	-0.226	Destabilizing	None	N	0.13	neutral	None	None	None	None	I
L/F	0.1324	likely_benign	0.1509	benign	-0.549	Destabilizing	0.82	D	0.167	neutral	N	0.465632192	None	None	I
L/G	0.2445	likely_benign	0.2889	benign	-0.534	Destabilizing	0.224	N	0.19	neutral	None	None	None	None	I
L/H	0.1392	likely_benign	0.159	benign	0.133	Stabilizing	0.674	D	0.137	neutral	None	None	None	None	I
L/I	0.0759	likely_benign	0.0795	benign	-0.24	Destabilizing	0.015	N	0.181	neutral	N	0.473174239	None	None	I
L/K	0.13	likely_benign	0.1249	benign	-0.246	Destabilizing	0.004	N	0.198	neutral	None	None	None	None	I
L/M	0.0851	likely_benign	0.0982	benign	-0.427	Destabilizing	0.644	D	0.195	neutral	None	None	None	None	I
L/N	0.1347	likely_benign	0.1435	benign	-0.094	Destabilizing	0.412	N	0.221	neutral	None	None	None	None	I
L/P	0.1581	likely_benign	0.1992	benign	-0.268	Destabilizing	0.587	D	0.256	neutral	None	None	None	None	I
L/Q	0.0696	likely_benign	0.0775	benign	-0.298	Destabilizing	0.127	N	0.219	neutral	None	None	None	None	I
L/R	0.1496	likely_benign	0.1501	benign	0.259	Stabilizing	0.218	N	0.226	neutral	None	None	None	None	I
L/S	0.094	likely_benign	0.12	benign	-0.503	Destabilizing	0.009	N	0.128	neutral	N	0.37146845	None	None	I
L/T	0.0942	likely_benign	0.1112	benign	-0.498	Destabilizing	None	N	0.106	neutral	None	None	None	None	I
L/V	0.0722	likely_benign	0.0825	benign	-0.268	Destabilizing	0.008	N	0.213	neutral	N	0.45683935	None	None	I
L/W	0.2522	likely_benign	0.2525	benign	-0.57	Destabilizing	0.988	D	0.159	neutral	None	None	None	None	I
L/Y	0.2983	likely_benign	0.2908	benign	-0.318	Destabilizing	0.414	N	0.207	neutral	None	None	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.