TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2143	6652;6653;6654	chr2:178775437;178775436;178775435	chr2:179640164;179640163;179640162
N2AB	2143	6652;6653;6654	chr2:178775437;178775436;178775435	chr2:179640164;179640163;179640162
N2A	2143	6652;6653;6654	chr2:178775437;178775436;178775435	chr2:179640164;179640163;179640162
N2B	2097	6514;6515;6516	chr2:178775437;178775436;178775435	chr2:179640164;179640163;179640162
Novex-1	2097	6514;6515;6516	chr2:178775437;178775436;178775435	chr2:179640164;179640163;179640162
Novex-2	2097	6514;6515;6516	chr2:178775437;178775436;178775435	chr2:179640164;179640163;179640162
Novex-3	2143	6652;6653;6654	chr2:178775437;178775436;178775435	chr2:179640164;179640163;179640162

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-10
• Domain position: 66
• Structural Position: 146
• Q(SASA): 0.277
• 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
A/V	rs1561277273	None	0.009	N	0.231	0.271	0.378322506985	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.82E-06	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
A/C	0.5075	ambiguous	0.6122	pathogenic	-0.715	Destabilizing	0.968	D	0.399	neutral	None	None	None	None	N
A/D	0.3142	likely_benign	0.4192	ambiguous	-0.639	Destabilizing	0.497	N	0.52	neutral	D	0.572259763	None	None	N
A/E	0.2609	likely_benign	0.3307	benign	-0.803	Destabilizing	0.567	D	0.344	neutral	None	None	None	None	N
A/F	0.3097	likely_benign	0.3935	ambiguous	-1.039	Destabilizing	0.726	D	0.551	neutral	None	None	None	None	N
A/G	0.1306	likely_benign	0.155	benign	-0.421	Destabilizing	0.124	N	0.378	neutral	D	0.534384836	None	None	N
A/H	0.462	ambiguous	0.5615	ambiguous	-0.462	Destabilizing	0.968	D	0.56	neutral	None	None	None	None	N
A/I	0.1561	likely_benign	0.1975	benign	-0.436	Destabilizing	0.396	N	0.355	neutral	None	None	None	None	N
A/K	0.4534	ambiguous	0.5576	ambiguous	-0.65	Destabilizing	0.567	D	0.353	neutral	None	None	None	None	N
A/L	0.1347	likely_benign	0.1624	benign	-0.436	Destabilizing	0.157	N	0.359	neutral	None	None	None	None	N
A/M	0.1612	likely_benign	0.1948	benign	-0.33	Destabilizing	0.909	D	0.429	neutral	None	None	None	None	N
A/N	0.1977	likely_benign	0.2413	benign	-0.296	Destabilizing	0.567	D	0.54	neutral	None	None	None	None	N
A/P	0.1619	likely_benign	0.1985	benign	-0.381	Destabilizing	0.002	N	0.26	neutral	N	0.449700225	None	None	N
A/Q	0.3147	likely_benign	0.3751	ambiguous	-0.631	Destabilizing	0.726	D	0.401	neutral	None	None	None	None	N
A/R	0.454	ambiguous	0.5586	ambiguous	-0.136	Destabilizing	0.567	D	0.406	neutral	None	None	None	None	N
A/S	0.0816	likely_benign	0.0883	benign	-0.484	Destabilizing	0.009	N	0.239	neutral	D	0.525146069	None	None	N
A/T	0.0765	likely_benign	0.0845	benign	-0.576	Destabilizing	0.124	N	0.381	neutral	D	0.534930137	None	None	N
A/V	0.0929	likely_benign	0.111	benign	-0.381	Destabilizing	0.009	N	0.231	neutral	N	0.515686195	None	None	N
A/W	0.6988	likely_pathogenic	0.7941	pathogenic	-1.155	Destabilizing	0.968	D	0.659	neutral	None	None	None	None	N
A/Y	0.4507	ambiguous	0.5579	ambiguous	-0.808	Destabilizing	0.89	D	0.55	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.