TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35743	107452;107453;107454	chr2:178528424;178528423;178528422	chr2:179393151;179393150;179393149
N2AB	34102	102529;102530;102531	chr2:178528424;178528423;178528422	chr2:179393151;179393150;179393149
N2A	33175	99748;99749;99750	chr2:178528424;178528423;178528422	chr2:179393151;179393150;179393149
N2B	26678	80257;80258;80259	chr2:178528424;178528423;178528422	chr2:179393151;179393150;179393149
Novex-1	26803	80632;80633;80634	chr2:178528424;178528423;178528422	chr2:179393151;179393150;179393149
Novex-2	26870	80833;80834;80835	chr2:178528424;178528423;178528422	chr2:179393151;179393150;179393149
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-168
• Domain position: 42
• Structural Position: 59
• Q(SASA): 0.5598
• 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
S/Y	None	None	0.966	N	0.407	0.268	0.711965941606	gnomAD-4.0.0	1.5944E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.44454E-05	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
S/A	0.0844	likely_benign	0.0854	benign	-0.133	Destabilizing	0.012	N	0.209	neutral	N	0.503832715	None	None	I
S/C	0.2344	likely_benign	0.2097	benign	-0.519	Destabilizing	0.997	D	0.373	neutral	N	0.509231996	None	None	I
S/D	0.4833	ambiguous	0.4718	ambiguous	0.112	Stabilizing	0.016	N	0.246	neutral	None	None	None	None	I
S/E	0.5913	likely_pathogenic	0.5528	ambiguous	0.016	Stabilizing	0.728	D	0.302	neutral	None	None	None	None	I
S/F	0.2373	likely_benign	0.2241	benign	-0.909	Destabilizing	0.934	D	0.408	neutral	N	0.521631829	None	None	I
S/G	0.1339	likely_benign	0.1291	benign	-0.169	Destabilizing	0.525	D	0.318	neutral	None	None	None	None	I
S/H	0.4327	ambiguous	0.3966	ambiguous	-0.446	Destabilizing	0.974	D	0.346	neutral	None	None	None	None	I
S/I	0.2232	likely_benign	0.2128	benign	-0.169	Destabilizing	0.728	D	0.383	neutral	None	None	None	None	I
S/K	0.7397	likely_pathogenic	0.7006	pathogenic	-0.369	Destabilizing	0.842	D	0.287	neutral	None	None	None	None	I
S/L	0.1258	likely_benign	0.1218	benign	-0.169	Destabilizing	0.728	D	0.371	neutral	None	None	None	None	I
S/M	0.2791	likely_benign	0.2649	benign	-0.297	Destabilizing	0.993	D	0.347	neutral	None	None	None	None	I
S/N	0.1795	likely_benign	0.1744	benign	-0.267	Destabilizing	0.067	N	0.225	neutral	None	None	None	None	I
S/P	0.1662	likely_benign	0.1511	benign	-0.134	Destabilizing	0.966	D	0.343	neutral	N	0.467335984	None	None	I
S/Q	0.5679	likely_pathogenic	0.5252	ambiguous	-0.415	Destabilizing	0.974	D	0.341	neutral	None	None	None	None	I
S/R	0.6305	likely_pathogenic	0.5904	pathogenic	-0.162	Destabilizing	0.974	D	0.354	neutral	None	None	None	None	I
S/T	0.0933	likely_benign	0.0907	benign	-0.343	Destabilizing	0.801	D	0.329	neutral	N	0.466295834	None	None	I
S/V	0.2202	likely_benign	0.2103	benign	-0.134	Destabilizing	0.016	N	0.269	neutral	None	None	None	None	I
S/W	0.4548	ambiguous	0.4295	ambiguous	-1.035	Destabilizing	0.998	D	0.544	neutral	None	None	None	None	I
S/Y	0.2254	likely_benign	0.2106	benign	-0.696	Destabilizing	0.966	D	0.407	neutral	N	0.504488863	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.