TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21512	64759;64760;64761	chr2:178585210;178585209;178585208	chr2:179449937;179449936;179449935
N2AB	19871	59836;59837;59838	chr2:178585210;178585209;178585208	chr2:179449937;179449936;179449935
N2A	18944	57055;57056;57057	chr2:178585210;178585209;178585208	chr2:179449937;179449936;179449935
N2B	12447	37564;37565;37566	chr2:178585210;178585209;178585208	chr2:179449937;179449936;179449935
Novex-1	12572	37939;37940;37941	chr2:178585210;178585209;178585208	chr2:179449937;179449936;179449935
Novex-2	12639	38140;38141;38142	chr2:178585210;178585209;178585208	chr2:179449937;179449936;179449935
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-124
• Domain position: 44
• Structural Position: 115
• Q(SASA): 0.3861
• 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
H/L	rs774754081	0.435	0.081	N	0.331	0.151	None	gnomAD-2.1.1	1.79E-05	None	None	None	None	N	None	2.06868E-04	0	None	0	0	None	0	None	0	0	0
H/L	rs774754081	0.435	0.081	N	0.331	0.151	None	gnomAD-3.1.2	6.57E-05	None	None	None	None	N	None	2.41255E-04	0	0	0	0	None	0	0	0	0	0
H/L	rs774754081	0.435	0.081	N	0.331	0.151	None	gnomAD-4.0.0	1.17773E-05	None	None	None	None	N	None	2.00272E-04	0	None	0	0	None	0	0	3.39128E-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
H/A	0.5154	ambiguous	0.3811	ambiguous	-0.306	Destabilizing	0.104	N	0.255	neutral	None	None	None	None	N
H/C	0.2761	likely_benign	0.1923	benign	0.364	Stabilizing	0.958	D	0.387	neutral	None	None	None	None	N
H/D	0.4804	ambiguous	0.3586	ambiguous	0.003	Stabilizing	0.175	N	0.319	neutral	N	0.437563998	None	None	N
H/E	0.549	ambiguous	0.4202	ambiguous	0.061	Stabilizing	0.055	N	0.214	neutral	None	None	None	None	N
H/F	0.4729	ambiguous	0.3755	ambiguous	0.485	Stabilizing	0.667	D	0.429	neutral	None	None	None	None	N
H/G	0.4878	ambiguous	0.3754	ambiguous	-0.638	Destabilizing	0.104	N	0.296	neutral	None	None	None	None	N
H/I	0.5297	ambiguous	0.3996	ambiguous	0.575	Stabilizing	0.667	D	0.489	neutral	None	None	None	None	N
H/K	0.3279	likely_benign	0.2508	benign	-0.18	Destabilizing	0.025	N	0.203	neutral	None	None	None	None	N
H/L	0.2311	likely_benign	0.1745	benign	0.575	Stabilizing	0.081	N	0.331	neutral	N	0.465924035	None	None	N
H/M	0.6615	likely_pathogenic	0.5627	ambiguous	0.443	Stabilizing	0.859	D	0.365	neutral	None	None	None	None	N
H/N	0.2066	likely_benign	0.1602	benign	-0.115	Destabilizing	0.081	N	0.261	neutral	N	0.43290754	None	None	N
H/P	0.5897	likely_pathogenic	0.4952	ambiguous	0.306	Stabilizing	0.301	N	0.426	neutral	N	0.477314465	None	None	N
H/Q	0.2594	likely_benign	0.1908	benign	0.041	Stabilizing	0.175	N	0.211	neutral	N	0.449666504	None	None	N
H/R	0.1002	likely_benign	0.0762	benign	-0.683	Destabilizing	None	N	0.069	neutral	N	0.325542427	None	None	N
H/S	0.3829	ambiguous	0.2864	benign	-0.179	Destabilizing	0.104	N	0.316	neutral	None	None	None	None	N
H/T	0.4357	ambiguous	0.3094	benign	-0.015	Destabilizing	0.104	N	0.324	neutral	None	None	None	None	N
H/V	0.4585	ambiguous	0.3414	ambiguous	0.306	Stabilizing	0.22	N	0.425	neutral	None	None	None	None	N
H/W	0.4813	ambiguous	0.4094	ambiguous	0.633	Stabilizing	0.958	D	0.354	neutral	None	None	None	None	N
H/Y	0.1515	likely_benign	0.1151	benign	0.882	Stabilizing	0.301	N	0.255	neutral	N	0.466270752	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.