TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15621	47086;47087;47088	chr2:178618689;178618688;178618687	chr2:179483416;179483415;179483414
N2AB	13980	42163;42164;42165	chr2:178618689;178618688;178618687	chr2:179483416;179483415;179483414
N2A	13053	39382;39383;39384	chr2:178618689;178618688;178618687	chr2:179483416;179483415;179483414
N2B	6556	19891;19892;19893	chr2:178618689;178618688;178618687	chr2:179483416;179483415;179483414
Novex-1	6681	20266;20267;20268	chr2:178618689;178618688;178618687	chr2:179483416;179483415;179483414
Novex-2	6748	20467;20468;20469	chr2:178618689;178618688;178618687	chr2:179483416;179483415;179483414
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-108
• Domain position: 54
• Structural Position: 137
• Q(SASA): 0.19
• 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/A	None	None	0.454	N	0.438	0.153	0.307648195649	gnomAD-4.0.0	1.59483E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86428E-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	0.077	likely_benign	0.0931	benign	-0.816	Destabilizing	0.454	N	0.438	neutral	N	0.514422284	None	None	N
S/C	0.1032	likely_benign	0.1107	benign	-0.655	Destabilizing	0.997	D	0.526	neutral	N	0.517619755	None	None	N
S/D	0.4504	ambiguous	0.5883	pathogenic	-1.397	Destabilizing	0.525	D	0.495	neutral	None	None	None	None	N
S/E	0.3985	ambiguous	0.4586	ambiguous	-1.213	Destabilizing	0.029	N	0.167	neutral	None	None	None	None	N
S/F	0.1684	likely_benign	0.2378	benign	-0.701	Destabilizing	0.966	D	0.584	neutral	N	0.516443155	None	None	N
S/G	0.1234	likely_benign	0.1692	benign	-1.207	Destabilizing	0.688	D	0.491	neutral	None	None	None	None	N
S/H	0.2667	likely_benign	0.2933	benign	-1.591	Destabilizing	0.991	D	0.547	neutral	None	None	None	None	N
S/I	0.1258	likely_benign	0.157	benign	0.17	Stabilizing	0.949	D	0.558	neutral	None	None	None	None	N
S/K	0.4818	ambiguous	0.5695	pathogenic	-0.27	Destabilizing	0.842	D	0.508	neutral	None	None	None	None	N
S/L	0.1182	likely_benign	0.1608	benign	0.17	Stabilizing	0.728	D	0.519	neutral	None	None	None	None	N
S/M	0.1764	likely_benign	0.2101	benign	0.067	Stabilizing	0.998	D	0.535	neutral	None	None	None	None	N
S/N	0.1367	likely_benign	0.1798	benign	-0.943	Destabilizing	0.842	D	0.509	neutral	None	None	None	None	N
S/P	0.928	likely_pathogenic	0.9693	pathogenic	-0.123	Destabilizing	0.966	D	0.536	neutral	N	0.51727274	None	None	N
S/Q	0.3635	ambiguous	0.3972	ambiguous	-0.726	Destabilizing	0.842	D	0.525	neutral	None	None	None	None	N
S/R	0.383	ambiguous	0.4554	ambiguous	-0.629	Destabilizing	0.949	D	0.534	neutral	None	None	None	None	N
S/T	0.0618	likely_benign	0.0732	benign	-0.615	Destabilizing	0.051	N	0.218	neutral	N	0.484291519	None	None	N
S/V	0.1292	likely_benign	0.1562	benign	-0.123	Destabilizing	0.728	D	0.52	neutral	None	None	None	None	N
S/W	0.364	ambiguous	0.4299	ambiguous	-0.948	Destabilizing	0.998	D	0.668	neutral	None	None	None	None	N
S/Y	0.1709	likely_benign	0.2154	benign	-0.492	Destabilizing	0.989	D	0.581	neutral	N	0.51727274	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.