TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27310	82153;82154;82155	chr2:178564204;178564203;178564202	chr2:179428931;179428930;179428929
N2AB	25669	77230;77231;77232	chr2:178564204;178564203;178564202	chr2:179428931;179428930;179428929
N2A	24742	74449;74450;74451	chr2:178564204;178564203;178564202	chr2:179428931;179428930;179428929
N2B	18245	54958;54959;54960	chr2:178564204;178564203;178564202	chr2:179428931;179428930;179428929
Novex-1	18370	55333;55334;55335	chr2:178564204;178564203;178564202	chr2:179428931;179428930;179428929
Novex-2	18437	55534;55535;55536	chr2:178564204;178564203;178564202	chr2:179428931;179428930;179428929
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-140
• Domain position: 33
• Structural Position: 49
• Q(SASA): 0.1676
• 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/P	rs794727454	None	0.001	N	0.269	0.145	0.0884992946249	gnomAD-4.0.0	1.36856E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79894E-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	0.0795	benign	-0.817	Destabilizing	None	N	0.221	neutral	N	0.469060341	None	None	N
S/C	0.0751	likely_benign	0.0761	benign	-0.409	Destabilizing	0.667	D	0.503	neutral	None	None	None	None	N
S/D	0.4399	ambiguous	0.4022	ambiguous	-0.61	Destabilizing	0.22	N	0.454	neutral	None	None	None	None	N
S/E	0.3762	ambiguous	0.3294	benign	-0.448	Destabilizing	0.22	N	0.453	neutral	None	None	None	None	N
S/F	0.1055	likely_benign	0.0975	benign	-0.748	Destabilizing	0.001	N	0.454	neutral	None	None	None	None	N
S/G	0.1264	likely_benign	0.121	benign	-1.198	Destabilizing	0.055	N	0.409	neutral	None	None	None	None	N
S/H	0.2352	likely_benign	0.228	benign	-1.491	Destabilizing	0.859	D	0.507	neutral	None	None	None	None	N
S/I	0.1203	likely_benign	0.1052	benign	0.141	Stabilizing	0.001	N	0.369	neutral	None	None	None	None	N
S/K	0.5422	ambiguous	0.489	ambiguous	0.036	Stabilizing	0.22	N	0.451	neutral	None	None	None	None	N
S/L	0.0554	likely_benign	0.0529	benign	0.141	Stabilizing	None	N	0.33	neutral	N	0.367335909	None	None	N
S/M	0.1131	likely_benign	0.102	benign	0.108	Stabilizing	0.497	N	0.524	neutral	None	None	None	None	N
S/N	0.1442	likely_benign	0.1337	benign	-0.485	Destabilizing	0.364	N	0.477	neutral	None	None	None	None	N
S/P	0.9515	likely_pathogenic	0.9465	pathogenic	-0.144	Destabilizing	0.001	N	0.269	neutral	N	0.466706025	None	None	N
S/Q	0.3517	ambiguous	0.3228	benign	-0.325	Destabilizing	0.667	D	0.503	neutral	None	None	None	None	N
S/R	0.4666	ambiguous	0.4301	ambiguous	-0.309	Destabilizing	0.667	D	0.541	neutral	None	None	None	None	N
S/T	0.0779	likely_benign	0.072	benign	-0.311	Destabilizing	0.081	N	0.432	neutral	N	0.430040593	None	None	N
S/V	0.1277	likely_benign	0.1131	benign	-0.144	Destabilizing	0.02	N	0.481	neutral	None	None	None	None	N
S/W	0.169	likely_benign	0.1701	benign	-0.858	Destabilizing	0.958	D	0.587	neutral	None	None	None	None	N
S/Y	0.0979	likely_benign	0.1004	benign	-0.442	Destabilizing	0.331	N	0.585	neutral	None	None	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.