TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22831	68716;68717;68718	chr2:178578024;178578023;178578022	chr2:179442751;179442750;179442749
N2AB	21190	63793;63794;63795	chr2:178578024;178578023;178578022	chr2:179442751;179442750;179442749
N2A	20263	61012;61013;61014	chr2:178578024;178578023;178578022	chr2:179442751;179442750;179442749
N2B	13766	41521;41522;41523	chr2:178578024;178578023;178578022	chr2:179442751;179442750;179442749
Novex-1	13891	41896;41897;41898	chr2:178578024;178578023;178578022	chr2:179442751;179442750;179442749
Novex-2	13958	42097;42098;42099	chr2:178578024;178578023;178578022	chr2:179442751;179442750;179442749
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-53
• Domain position: 89
• Structural Position: 122
• Q(SASA): 0.6511
• 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/P	None	None	0.006	N	0.461	0.168	0.408444019923	gnomAD-4.0.0	6.37048E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.14419E-05	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	0.1264	likely_benign	0.1239	benign	-0.807	Destabilizing	0.505	D	0.527	neutral	None	None	None	None	I
L/C	0.4222	ambiguous	0.4079	ambiguous	-0.686	Destabilizing	0.995	D	0.594	neutral	None	None	None	None	I
L/D	0.4727	ambiguous	0.4759	ambiguous	-0.201	Destabilizing	0.946	D	0.649	prob.neutral	None	None	None	None	I
L/E	0.2386	likely_benign	0.2325	benign	-0.277	Destabilizing	0.712	D	0.603	neutral	None	None	None	None	I
L/F	0.1134	likely_benign	0.1074	benign	-0.695	Destabilizing	0.982	D	0.563	neutral	None	None	None	None	I
L/G	0.3231	likely_benign	0.3113	benign	-0.997	Destabilizing	0.712	D	0.625	neutral	None	None	None	None	I
L/H	0.1619	likely_benign	0.1522	benign	-0.182	Destabilizing	0.995	D	0.625	neutral	None	None	None	None	I
L/I	0.084	likely_benign	0.0857	benign	-0.418	Destabilizing	0.791	D	0.466	neutral	N	0.473743803	None	None	I
L/K	0.1655	likely_benign	0.1604	benign	-0.473	Destabilizing	0.032	N	0.377	neutral	None	None	None	None	I
L/M	0.0944	likely_benign	0.0892	benign	-0.45	Destabilizing	0.982	D	0.575	neutral	None	None	None	None	I
L/N	0.2103	likely_benign	0.2143	benign	-0.274	Destabilizing	0.946	D	0.654	prob.neutral	None	None	None	None	I
L/P	0.107	likely_benign	0.1128	benign	-0.514	Destabilizing	0.006	N	0.461	neutral	N	0.402880995	None	None	I
L/Q	0.0997	likely_benign	0.0917	benign	-0.488	Destabilizing	0.868	D	0.634	neutral	N	0.452963099	None	None	I
L/R	0.1609	likely_benign	0.1485	benign	0.113	Stabilizing	0.002	N	0.345	neutral	N	0.447999996	None	None	I
L/S	0.1356	likely_benign	0.1358	benign	-0.776	Destabilizing	0.712	D	0.578	neutral	None	None	None	None	I
L/T	0.1399	likely_benign	0.1369	benign	-0.74	Destabilizing	0.834	D	0.531	neutral	None	None	None	None	I
L/V	0.0785	likely_benign	0.0766	benign	-0.514	Destabilizing	0.791	D	0.413	neutral	N	0.46279609	None	None	I
L/W	0.2516	likely_benign	0.2388	benign	-0.696	Destabilizing	0.995	D	0.657	prob.neutral	None	None	None	None	I
L/Y	0.2471	likely_benign	0.2377	benign	-0.466	Destabilizing	0.982	D	0.624	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.