TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21051	63376;63377;63378	chr2:178588574;178588573;178588572	chr2:179453301;179453300;179453299
N2AB	19410	58453;58454;58455	chr2:178588574;178588573;178588572	chr2:179453301;179453300;179453299
N2A	18483	55672;55673;55674	chr2:178588574;178588573;178588572	chr2:179453301;179453300;179453299
N2B	11986	36181;36182;36183	chr2:178588574;178588573;178588572	chr2:179453301;179453300;179453299
Novex-1	12111	36556;36557;36558	chr2:178588574;178588573;178588572	chr2:179453301;179453300;179453299
Novex-2	12178	36757;36758;36759	chr2:178588574;178588573;178588572	chr2:179453301;179453300;179453299
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Fn3-40
• Domain position: 89
• Structural Position: 122
• Q(SASA): 0.7401
• 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	None	None	0.002	N	0.142	0.087	0.356690202451	gnomAD-4.0.0	2.1566E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.77745E-06	0	0
L/S	None	None	0.361	N	0.407	0.099	0.448099371145	gnomAD-4.0.0	1.78861E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.97543E-05	0	0	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	0.1159	likely_benign	0.1063	benign	-0.99	Destabilizing	0.134	N	0.404	neutral	None	None	None	None	I
L/C	0.3265	likely_benign	0.3483	ambiguous	-0.721	Destabilizing	0.984	D	0.393	neutral	None	None	None	None	I
L/D	0.3337	likely_benign	0.2983	benign	-0.22	Destabilizing	0.842	D	0.398	neutral	None	None	None	None	I
L/E	0.1778	likely_benign	0.1695	benign	-0.285	Destabilizing	0.428	N	0.413	neutral	None	None	None	None	I
L/F	0.091	likely_benign	0.092	benign	-0.782	Destabilizing	0.002	N	0.142	neutral	N	0.52105496	None	None	I
L/G	0.2658	likely_benign	0.2676	benign	-1.212	Destabilizing	0.001	N	0.255	neutral	None	None	None	None	I
L/H	0.148	likely_benign	0.1535	benign	-0.351	Destabilizing	0.984	D	0.319	neutral	None	None	None	None	I
L/I	0.0849	likely_benign	0.0837	benign	-0.506	Destabilizing	0.272	N	0.341	neutral	None	None	None	None	I
L/K	0.1676	likely_benign	0.1812	benign	-0.537	Destabilizing	0.004	N	0.194	neutral	None	None	None	None	I
L/M	0.0921	likely_benign	0.0913	benign	-0.458	Destabilizing	0.8	D	0.459	neutral	N	0.472839726	None	None	I
L/N	0.1804	likely_benign	0.1589	benign	-0.295	Destabilizing	0.724	D	0.398	neutral	None	None	None	None	I
L/P	0.0916	likely_benign	0.0888	benign	-0.634	Destabilizing	0.942	D	0.406	neutral	None	None	None	None	I
L/Q	0.0966	likely_benign	0.1013	benign	-0.521	Destabilizing	0.724	D	0.429	neutral	None	None	None	None	I
L/R	0.1593	likely_benign	0.1895	benign	0.068	Stabilizing	0.272	N	0.433	neutral	None	None	None	None	I
L/S	0.1212	likely_benign	0.1098	benign	-0.864	Destabilizing	0.361	N	0.407	neutral	N	0.447690565	None	None	I
L/T	0.1373	likely_benign	0.1261	benign	-0.814	Destabilizing	0.603	D	0.461	neutral	None	None	None	None	I
L/V	0.0753	likely_benign	0.076	benign	-0.634	Destabilizing	0.22	N	0.321	neutral	N	0.446903918	None	None	I
L/W	0.1996	likely_benign	0.2225	benign	-0.758	Destabilizing	0.979	D	0.346	neutral	N	0.510011247	None	None	I
L/Y	0.1771	likely_benign	0.174	benign	-0.539	Destabilizing	0.568	D	0.47	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.