TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7045	21358;21359;21360	chr2:178724126;178724125;178724124	chr2:179588853;179588852;179588851
N2AB	6728	20407;20408;20409	chr2:178724126;178724125;178724124	chr2:179588853;179588852;179588851
N2A	5801	17626;17627;17628	chr2:178724126;178724125;178724124	chr2:179588853;179588852;179588851
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-55
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.4708
• Predicted PPI site: N

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/T	rs921127943	None	0.891	N	0.277	0.14	0.202086224978	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
S/T	rs921127943	None	0.891	N	0.277	0.14	0.202086224978	gnomAD-4.0.0	5.13799E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.60343E-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
S/A	0.081	likely_benign	0.0867	benign	-0.593	Destabilizing	0.625	D	0.317	neutral	N	0.49977134	None	None	N
S/C	0.1273	likely_benign	0.1271	benign	-0.377	Destabilizing	0.997	D	0.355	neutral	D	0.526740366	None	None	N
S/D	0.4988	ambiguous	0.4725	ambiguous	0.445	Stabilizing	0.915	D	0.334	neutral	None	None	None	None	N
S/E	0.5226	ambiguous	0.4911	ambiguous	0.398	Stabilizing	0.842	D	0.273	neutral	None	None	None	None	N
S/F	0.1149	likely_benign	0.1027	benign	-1.006	Destabilizing	0.028	N	0.256	neutral	D	0.526325573	None	None	N
S/G	0.1383	likely_benign	0.1418	benign	-0.771	Destabilizing	0.915	D	0.255	neutral	None	None	None	None	N
S/H	0.2905	likely_benign	0.2423	benign	-1.202	Destabilizing	0.974	D	0.35	neutral	None	None	None	None	N
S/I	0.128	likely_benign	0.1334	benign	-0.245	Destabilizing	0.728	D	0.297	neutral	None	None	None	None	N
S/K	0.573	likely_pathogenic	0.517	ambiguous	-0.381	Destabilizing	0.067	N	0.162	neutral	None	None	None	None	N
S/L	0.0921	likely_benign	0.0927	benign	-0.245	Destabilizing	0.016	N	0.269	neutral	None	None	None	None	N
S/M	0.2109	likely_benign	0.2094	benign	-0.06	Destabilizing	0.949	D	0.353	neutral	None	None	None	None	N
S/N	0.2018	likely_benign	0.1935	benign	-0.222	Destabilizing	0.915	D	0.367	neutral	None	None	None	None	N
S/P	0.7922	likely_pathogenic	0.8362	pathogenic	-0.329	Destabilizing	0.989	D	0.372	neutral	N	0.511256231	None	None	N
S/Q	0.4443	ambiguous	0.4124	ambiguous	-0.395	Destabilizing	0.949	D	0.381	neutral	None	None	None	None	N
S/R	0.416	ambiguous	0.3668	ambiguous	-0.268	Destabilizing	0.904	D	0.365	neutral	None	None	None	None	N
S/T	0.0819	likely_benign	0.085	benign	-0.346	Destabilizing	0.891	D	0.277	neutral	N	0.507873098	None	None	N
S/V	0.1299	likely_benign	0.1353	benign	-0.329	Destabilizing	0.728	D	0.279	neutral	None	None	None	None	N
S/W	0.2828	likely_benign	0.2568	benign	-0.96	Destabilizing	0.998	D	0.401	neutral	None	None	None	None	N
S/Y	0.1307	likely_benign	0.1236	benign	-0.683	Destabilizing	0.111	N	0.255	neutral	N	0.498000595	None	None	N

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.