TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14738	44437;44438;44439	chr2:178630310;178630309;178630308	chr2:179495037;179495036;179495035
N2AB	13097	39514;39515;39516	chr2:178630310;178630309;178630308	chr2:179495037;179495036;179495035
N2A	12170	36733;36734;36735	chr2:178630310;178630309;178630308	chr2:179495037;179495036;179495035
N2B	5673	17242;17243;17244	chr2:178630310;178630309;178630308	chr2:179495037;179495036;179495035
Novex-1	5798	17617;17618;17619	chr2:178630310;178630309;178630308	chr2:179495037;179495036;179495035
Novex-2	5865	17818;17819;17820	chr2:178630310;178630309;178630308	chr2:179495037;179495036;179495035
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-98
• Domain position: 64
• Structural Position: 146
• Q(SASA): 0.4754
• 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
L/V	rs2154219916	None	0.067	N	0.229	0.047	0.233150807113	gnomAD-4.0.0	6.84516E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99735E-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
L/A	0.3508	ambiguous	0.4428	ambiguous	-1.42	Destabilizing	0.745	D	0.272	neutral	None	None	None	None	N
L/C	0.7036	likely_pathogenic	0.7692	pathogenic	-0.778	Destabilizing	0.998	D	0.311	neutral	None	None	None	None	N
L/D	0.8236	likely_pathogenic	0.8572	pathogenic	-0.975	Destabilizing	0.981	D	0.528	neutral	None	None	None	None	N
L/E	0.4668	ambiguous	0.5185	ambiguous	-1.034	Destabilizing	0.876	D	0.425	neutral	None	None	None	None	N
L/F	0.2814	likely_benign	0.3114	benign	-1.168	Destabilizing	0.961	D	0.355	neutral	None	None	None	None	N
L/G	0.6498	likely_pathogenic	0.7251	pathogenic	-1.672	Destabilizing	0.935	D	0.463	neutral	None	None	None	None	N
L/H	0.3785	ambiguous	0.4361	ambiguous	-0.865	Destabilizing	0.998	D	0.407	neutral	None	None	None	None	N
L/I	0.1335	likely_benign	0.1572	benign	-0.833	Destabilizing	0.78	D	0.316	neutral	None	None	None	None	N
L/K	0.3171	likely_benign	0.3738	ambiguous	-0.966	Destabilizing	0.087	N	0.189	neutral	None	None	None	None	N
L/M	0.1346	likely_benign	0.1519	benign	-0.568	Destabilizing	0.325	N	0.251	neutral	N	0.438912078	None	None	N
L/N	0.5632	ambiguous	0.6408	pathogenic	-0.683	Destabilizing	0.981	D	0.529	neutral	None	None	None	None	N
L/P	0.2705	likely_benign	0.3598	ambiguous	-0.997	Destabilizing	0.991	D	0.535	neutral	N	0.436910263	None	None	N
L/Q	0.2059	likely_benign	0.2561	benign	-0.951	Destabilizing	0.949	D	0.421	neutral	N	0.420371489	None	None	N
L/R	0.2484	likely_benign	0.2877	benign	-0.265	Destabilizing	0.142	N	0.187	neutral	N	0.43516344	None	None	N
L/S	0.4353	ambiguous	0.5399	ambiguous	-1.196	Destabilizing	0.876	D	0.369	neutral	None	None	None	None	N
L/T	0.3292	likely_benign	0.4016	ambiguous	-1.149	Destabilizing	0.876	D	0.339	neutral	None	None	None	None	N
L/V	0.1435	likely_benign	0.1759	benign	-0.997	Destabilizing	0.067	N	0.229	neutral	N	0.437293845	None	None	N
L/W	0.3503	ambiguous	0.3502	ambiguous	-1.174	Destabilizing	0.998	D	0.473	neutral	None	None	None	None	N
L/Y	0.5403	ambiguous	0.5886	pathogenic	-0.976	Destabilizing	0.994	D	0.418	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.