TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18210	54853;54854;54855	chr2:178604059;178604058;178604057	chr2:179468786;179468785;179468784
N2AB	16569	49930;49931;49932	chr2:178604059;178604058;178604057	chr2:179468786;179468785;179468784
N2A	15642	47149;47150;47151	chr2:178604059;178604058;178604057	chr2:179468786;179468785;179468784
N2B	9145	27658;27659;27660	chr2:178604059;178604058;178604057	chr2:179468786;179468785;179468784
Novex-1	9270	28033;28034;28035	chr2:178604059;178604058;178604057	chr2:179468786;179468785;179468784
Novex-2	9337	28234;28235;28236	chr2:178604059;178604058;178604057	chr2:179468786;179468785;179468784
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-20
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.2321
• 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/I	None	None	0.055	N	0.363	0.196	0.436348499334	gnomAD-4.0.0	6.84561E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99896E-07	0	0
S/T	None	None	None	N	0.117	0.193	0.193865811164	gnomAD-4.0.0	6.84561E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99896E-07	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	0.1161	likely_benign	0.0998	benign	-0.487	Destabilizing	0.003	N	0.243	neutral	None	None	None	None	N
S/C	0.0927	likely_benign	0.095	benign	-0.418	Destabilizing	0.56	D	0.386	neutral	N	0.47278759	None	None	N
S/D	0.5356	ambiguous	0.479	ambiguous	0.151	Stabilizing	0.031	N	0.3	neutral	None	None	None	None	N
S/E	0.6136	likely_pathogenic	0.5485	ambiguous	0.103	Stabilizing	0.061	N	0.277	neutral	None	None	None	None	N
S/F	0.3708	ambiguous	0.3005	benign	-0.809	Destabilizing	0.628	D	0.441	neutral	None	None	None	None	N
S/G	0.0814	likely_benign	0.0681	benign	-0.672	Destabilizing	None	N	0.121	neutral	N	0.463548239	None	None	N
S/H	0.3969	ambiguous	0.3569	ambiguous	-1.095	Destabilizing	0.628	D	0.389	neutral	None	None	None	None	N
S/I	0.2441	likely_benign	0.2021	benign	-0.117	Destabilizing	0.055	N	0.363	neutral	N	0.516884078	None	None	N
S/K	0.7162	likely_pathogenic	0.6777	pathogenic	-0.663	Destabilizing	0.031	N	0.275	neutral	None	None	None	None	N
S/L	0.158	likely_benign	0.1287	benign	-0.117	Destabilizing	0.031	N	0.271	neutral	None	None	None	None	N
S/M	0.2527	likely_benign	0.2171	benign	-0.045	Destabilizing	0.628	D	0.385	neutral	None	None	None	None	N
S/N	0.1676	likely_benign	0.1459	benign	-0.448	Destabilizing	0.024	N	0.308	neutral	N	0.483288793	None	None	N
S/P	0.7043	likely_pathogenic	0.6732	pathogenic	-0.208	Destabilizing	0.136	N	0.349	neutral	None	None	None	None	N
S/Q	0.5205	ambiguous	0.457	ambiguous	-0.603	Destabilizing	0.136	N	0.353	neutral	None	None	None	None	N
S/R	0.6913	likely_pathogenic	0.6397	pathogenic	-0.496	Destabilizing	0.106	N	0.343	neutral	N	0.488908043	None	None	N
S/T	0.1274	likely_benign	0.1067	benign	-0.513	Destabilizing	None	N	0.117	neutral	N	0.437479145	None	None	N
S/V	0.2314	likely_benign	0.1881	benign	-0.208	Destabilizing	0.031	N	0.279	neutral	None	None	None	None	N
S/W	0.4853	ambiguous	0.4277	ambiguous	-0.818	Destabilizing	0.864	D	0.411	neutral	None	None	None	None	N
S/Y	0.2899	likely_benign	0.2583	benign	-0.557	Destabilizing	0.628	D	0.415	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.