TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1521	4786;4787;4788	chr2:178777504;178777503;178777502	chr2:179642231;179642230;179642229
N2AB	1521	4786;4787;4788	chr2:178777504;178777503;178777502	chr2:179642231;179642230;179642229
N2A	1521	4786;4787;4788	chr2:178777504;178777503;178777502	chr2:179642231;179642230;179642229
N2B	1475	4648;4649;4650	chr2:178777504;178777503;178777502	chr2:179642231;179642230;179642229
Novex-1	1475	4648;4649;4650	chr2:178777504;178777503;178777502	chr2:179642231;179642230;179642229
Novex-2	1475	4648;4649;4650	chr2:178777504;178777503;178777502	chr2:179642231;179642230;179642229
Novex-3	1521	4786;4787;4788	chr2:178777504;178777503;178777502	chr2:179642231;179642230;179642229

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-6
• Domain position: 65
• Structural Position: 145
• Q(SASA): 0.3519
• 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/I	None	None	0.012	D	0.402	0.109	0.29132392195	gnomAD-4.0.0	2.40067E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.62503E-06	0	0
T/P	rs1574674545	None	0.055	D	0.434	0.219	0.0806252709748	gnomAD-4.0.0	1.59124E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.0248E-05

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	0.0676	likely_benign	0.0684	benign	-0.727	Destabilizing	None	N	0.103	neutral	N	0.508355694	None	None	I
T/C	0.3435	ambiguous	0.3173	benign	-0.466	Destabilizing	0.356	N	0.398	neutral	None	None	None	None	I
T/D	0.2619	likely_benign	0.2486	benign	-0.322	Destabilizing	0.038	N	0.436	neutral	None	None	None	None	I
T/E	0.1967	likely_benign	0.188	benign	-0.353	Destabilizing	0.016	N	0.427	neutral	None	None	None	None	I
T/F	0.1668	likely_benign	0.1539	benign	-0.982	Destabilizing	0.072	N	0.524	neutral	None	None	None	None	I
T/G	0.1561	likely_benign	0.1499	benign	-0.94	Destabilizing	0.016	N	0.361	neutral	None	None	None	None	I
T/H	0.195	likely_benign	0.1741	benign	-1.295	Destabilizing	0.214	N	0.455	neutral	None	None	None	None	I
T/I	0.0978	likely_benign	0.0971	benign	-0.26	Destabilizing	0.012	N	0.402	neutral	D	0.537603329	None	None	I
T/K	0.1179	likely_benign	0.1075	benign	-0.685	Destabilizing	0.012	N	0.406	neutral	N	0.498872838	None	None	I
T/L	0.0639	likely_benign	0.062	benign	-0.26	Destabilizing	None	N	0.102	neutral	None	None	None	None	I
T/M	0.066	likely_benign	0.067	benign	0.133	Stabilizing	0.001	N	0.103	neutral	None	None	None	None	I
T/N	0.0914	likely_benign	0.0907	benign	-0.586	Destabilizing	None	N	0.151	neutral	None	None	None	None	I
T/P	0.3583	ambiguous	0.424	ambiguous	-0.385	Destabilizing	0.055	N	0.434	neutral	D	0.659602375	None	None	I
T/Q	0.1491	likely_benign	0.1391	benign	-0.842	Destabilizing	0.072	N	0.472	neutral	None	None	None	None	I
T/R	0.1147	likely_benign	0.1056	benign	-0.393	Destabilizing	0.055	N	0.437	neutral	N	0.452945221	None	None	I
T/S	0.0805	likely_benign	0.0782	benign	-0.833	Destabilizing	None	N	0.152	neutral	N	0.498798882	None	None	I
T/V	0.0822	likely_benign	0.0803	benign	-0.385	Destabilizing	None	N	0.132	neutral	None	None	None	None	I
T/W	0.5144	ambiguous	0.4946	ambiguous	-0.907	Destabilizing	0.864	D	0.439	neutral	None	None	None	None	I
T/Y	0.2368	likely_benign	0.2214	benign	-0.662	Destabilizing	0.356	N	0.519	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.