TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4858	14797;14798;14799	chr2:178735874;178735873;178735872	chr2:179600601;179600600;179600599
N2AB	4541	13846;13847;13848	chr2:178735874;178735873;178735872	chr2:179600601;179600600;179600599
N2A	3614	11065;11066;11067	chr2:178735874;178735873;178735872	chr2:179600601;179600600;179600599
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: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-31
• Domain position: 64
• Structural Position: 145
• Q(SASA): 0.2958
• 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
T/S	rs2081354978	None	0.023	N	0.121	0.071	0.251639045875	gnomAD-4.0.0	1.59116E-06	None	None	None	None	I	None	0	2.28655E-05	None	0	0	None	0	0	0	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
T/A	0.1105	likely_benign	0.0994	benign	-0.74	Destabilizing	0.01	N	0.094	neutral	N	0.501928201	None	None	I
T/C	0.5126	ambiguous	0.4403	ambiguous	-0.374	Destabilizing	0.995	D	0.413	neutral	None	None	None	None	I
T/D	0.3355	likely_benign	0.2815	benign	0.056	Stabilizing	0.329	N	0.425	neutral	None	None	None	None	I
T/E	0.2992	likely_benign	0.2571	benign	0.051	Stabilizing	0.013	N	0.113	neutral	None	None	None	None	I
T/F	0.3783	ambiguous	0.3085	benign	-0.858	Destabilizing	0.981	D	0.497	neutral	None	None	None	None	I
T/G	0.2432	likely_benign	0.1952	benign	-0.993	Destabilizing	0.329	N	0.463	neutral	None	None	None	None	I
T/H	0.2726	likely_benign	0.2236	benign	-1.268	Destabilizing	0.944	D	0.477	neutral	None	None	None	None	I
T/I	0.3523	ambiguous	0.3093	benign	-0.165	Destabilizing	0.927	D	0.439	neutral	N	0.496818015	None	None	I
T/K	0.19	likely_benign	0.1607	benign	-0.612	Destabilizing	0.329	N	0.415	neutral	None	None	None	None	I
T/L	0.1504	likely_benign	0.1284	benign	-0.165	Destabilizing	0.704	D	0.416	neutral	None	None	None	None	I
T/M	0.1277	likely_benign	0.1114	benign	0.095	Stabilizing	0.981	D	0.427	neutral	None	None	None	None	I
T/N	0.1189	likely_benign	0.1018	benign	-0.508	Destabilizing	0.642	D	0.309	neutral	N	0.494406951	None	None	I
T/P	0.3253	likely_benign	0.2844	benign	-0.324	Destabilizing	0.784	D	0.437	neutral	D	0.556692335	None	None	I
T/Q	0.1925	likely_benign	0.1696	benign	-0.644	Destabilizing	0.085	N	0.132	neutral	None	None	None	None	I
T/R	0.1609	likely_benign	0.1372	benign	-0.417	Destabilizing	0.704	D	0.44	neutral	None	None	None	None	I
T/S	0.1118	likely_benign	0.0961	benign	-0.81	Destabilizing	0.023	N	0.121	neutral	N	0.466986724	None	None	I
T/V	0.2616	likely_benign	0.2323	benign	-0.324	Destabilizing	0.704	D	0.302	neutral	None	None	None	None	I
T/W	0.715	likely_pathogenic	0.6307	pathogenic	-0.804	Destabilizing	0.995	D	0.499	neutral	None	None	None	None	I
T/Y	0.4024	ambiguous	0.3329	benign	-0.565	Destabilizing	0.981	D	0.504	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.