TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28414	85465;85466;85467	chr2:178560892;178560891;178560890	chr2:179425619;179425618;179425617
N2AB	26773	80542;80543;80544	chr2:178560892;178560891;178560890	chr2:179425619;179425618;179425617
N2A	25846	77761;77762;77763	chr2:178560892;178560891;178560890	chr2:179425619;179425618;179425617
N2B	19349	58270;58271;58272	chr2:178560892;178560891;178560890	chr2:179425619;179425618;179425617
Novex-1	19474	58645;58646;58647	chr2:178560892;178560891;178560890	chr2:179425619;179425618;179425617
Novex-2	19541	58846;58847;58848	chr2:178560892;178560891;178560890	chr2:179425619;179425618;179425617
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-143
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.2305
• 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	rs775228620	-2.587	None	N	0.38	0.131	0.289474373501	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
L/S	rs775228620	-2.587	None	N	0.38	0.131	0.289474373501	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/S	rs775228620	-2.587	None	N	0.38	0.131	0.289474373501	gnomAD-4.0.0	6.57108E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.4699E-05	0	0
L/W	None	None	0.828	N	0.593	0.225	0.591025817267	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1053	likely_benign	0.1183	benign	-2.678	Highly Destabilizing	None	N	0.271	neutral	None	None	None	None	I
L/C	0.2376	likely_benign	0.2563	benign	-1.985	Destabilizing	0.356	N	0.563	neutral	None	None	None	None	I
L/D	0.491	ambiguous	0.4959	ambiguous	-3.292	Highly Destabilizing	0.072	N	0.529	neutral	None	None	None	None	I
L/E	0.2081	likely_benign	0.2208	benign	-3.12	Highly Destabilizing	0.038	N	0.482	neutral	None	None	None	None	I
L/F	0.1001	likely_benign	0.0955	benign	-1.602	Destabilizing	0.055	N	0.529	neutral	N	0.513894993	None	None	I
L/G	0.3656	ambiguous	0.3767	ambiguous	-3.156	Highly Destabilizing	0.016	N	0.433	neutral	None	None	None	None	I
L/H	0.1292	likely_benign	0.1287	benign	-2.613	Highly Destabilizing	0.356	N	0.587	neutral	None	None	None	None	I
L/I	0.0621	likely_benign	0.0615	benign	-1.299	Destabilizing	0.006	N	0.375	neutral	None	None	None	None	I
L/K	0.1854	likely_benign	0.2049	benign	-2.113	Highly Destabilizing	0.038	N	0.473	neutral	None	None	None	None	I
L/M	0.0692	likely_benign	0.069	benign	-1.208	Destabilizing	0.002	N	0.375	neutral	N	0.481918648	None	None	I
L/N	0.2027	likely_benign	0.2146	benign	-2.37	Highly Destabilizing	0.038	N	0.538	neutral	None	None	None	None	I
L/P	0.9507	likely_pathogenic	0.9475	pathogenic	-1.741	Destabilizing	0.072	N	0.585	neutral	None	None	None	None	I
L/Q	0.0946	likely_benign	0.096	benign	-2.307	Highly Destabilizing	0.214	N	0.609	neutral	None	None	None	None	I
L/R	0.1478	likely_benign	0.1547	benign	-1.69	Destabilizing	0.072	N	0.585	neutral	None	None	None	None	I
L/S	0.1029	likely_benign	0.1092	benign	-2.961	Highly Destabilizing	None	N	0.38	neutral	N	0.404724514	None	None	I
L/T	0.0723	likely_benign	0.0821	benign	-2.669	Highly Destabilizing	None	N	0.267	neutral	None	None	None	None	I
L/V	0.0624	likely_benign	0.0612	benign	-1.741	Destabilizing	None	N	0.173	neutral	N	0.410287836	None	None	I
L/W	0.2129	likely_benign	0.1961	benign	-2.051	Highly Destabilizing	0.828	D	0.593	neutral	N	0.487618567	None	None	I
L/Y	0.2042	likely_benign	0.2004	benign	-1.838	Destabilizing	0.356	N	0.578	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.