TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23458	70597;70598;70599	chr2:178575760;178575759;178575758	chr2:179440487;179440486;179440485
N2AB	21817	65674;65675;65676	chr2:178575760;178575759;178575758	chr2:179440487;179440486;179440485
N2A	20890	62893;62894;62895	chr2:178575760;178575759;178575758	chr2:179440487;179440486;179440485
N2B	14393	43402;43403;43404	chr2:178575760;178575759;178575758	chr2:179440487;179440486;179440485
Novex-1	14518	43777;43778;43779	chr2:178575760;178575759;178575758	chr2:179440487;179440486;179440485
Novex-2	14585	43978;43979;43980	chr2:178575760;178575759;178575758	chr2:179440487;179440486;179440485
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Fn3-58
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.5644
• Predicted PPI site: I

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/F	rs1709865828	None	0.884	N	0.503	0.199	0.51754283126	gnomAD-4.0.0	1.5919E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02572E-05

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	0.2123	likely_benign	0.2044	benign	-1.549	Destabilizing	0.543	D	0.406	neutral	None	None	None	None	I
L/C	0.5463	ambiguous	0.5775	pathogenic	-0.949	Destabilizing	0.996	D	0.567	neutral	None	None	None	None	I
L/D	0.7586	likely_pathogenic	0.7871	pathogenic	-1.157	Destabilizing	0.59	D	0.588	neutral	None	None	None	None	I
L/E	0.4971	ambiguous	0.5348	ambiguous	-1.126	Destabilizing	0.009	N	0.407	neutral	None	None	None	None	I
L/F	0.1684	likely_benign	0.1904	benign	-1.033	Destabilizing	0.884	D	0.503	neutral	N	0.467956768	None	None	I
L/G	0.5428	ambiguous	0.5415	ambiguous	-1.866	Destabilizing	0.742	D	0.587	neutral	None	None	None	None	I
L/H	0.2883	likely_benign	0.3033	benign	-0.897	Destabilizing	0.983	D	0.541	neutral	N	0.419221458	None	None	I
L/I	0.0966	likely_benign	0.1007	benign	-0.74	Destabilizing	0.012	N	0.103	neutral	N	0.392477574	None	None	I
L/K	0.4008	ambiguous	0.4206	ambiguous	-1.065	Destabilizing	0.59	D	0.535	neutral	None	None	None	None	I
L/M	0.0928	likely_benign	0.097	benign	-0.72	Destabilizing	0.101	N	0.136	neutral	None	None	None	None	I
L/N	0.3409	ambiguous	0.3456	ambiguous	-0.967	Destabilizing	0.91	D	0.585	neutral	None	None	None	None	I
L/P	0.1684	likely_benign	0.1524	benign	-0.981	Destabilizing	0.939	D	0.576	neutral	N	0.250018453	None	None	I
L/Q	0.2069	likely_benign	0.2049	benign	-1.093	Destabilizing	0.835	D	0.6	neutral	None	None	None	None	I
L/R	0.3695	ambiguous	0.3965	ambiguous	-0.494	Destabilizing	0.884	D	0.6	neutral	N	0.380009709	None	None	I
L/S	0.2594	likely_benign	0.2607	benign	-1.521	Destabilizing	0.742	D	0.505	neutral	None	None	None	None	I
L/T	0.1975	likely_benign	0.2052	benign	-1.364	Destabilizing	0.742	D	0.474	neutral	None	None	None	None	I
L/V	0.0957	likely_benign	0.0952	benign	-0.981	Destabilizing	0.164	N	0.271	neutral	N	0.358095642	None	None	I
L/W	0.4329	ambiguous	0.4736	ambiguous	-1.088	Destabilizing	0.996	D	0.572	neutral	None	None	None	None	I
L/Y	0.3978	ambiguous	0.419	ambiguous	-0.872	Destabilizing	0.953	D	0.588	neutral	None	None	None	None	I

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.