TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25626	77101;77102;77103	chr2:178569256;178569255;178569254	chr2:179433983;179433982;179433981
N2AB	23985	72178;72179;72180	chr2:178569256;178569255;178569254	chr2:179433983;179433982;179433981
N2A	23058	69397;69398;69399	chr2:178569256;178569255;178569254	chr2:179433983;179433982;179433981
N2B	16561	49906;49907;49908	chr2:178569256;178569255;178569254	chr2:179433983;179433982;179433981
Novex-1	16686	50281;50282;50283	chr2:178569256;178569255;178569254	chr2:179433983;179433982;179433981
Novex-2	16753	50482;50483;50484	chr2:178569256;178569255;178569254	chr2:179433983;179433982;179433981
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: Fn3-74
• Domain position: 26
• Structural Position: 28
• Q(SASA): 1.0087
• 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	0.757	N	0.331	0.185	0.246773566709	gnomAD-4.0.0	6.88414E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.03347E-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	0.1593	likely_benign	0.1776	benign	-0.576	Destabilizing	0.002	N	0.162	neutral	None	None	None	None	I
L/C	0.496	ambiguous	0.5513	ambiguous	-0.673	Destabilizing	0.992	D	0.303	neutral	None	None	None	None	I
L/D	0.5116	ambiguous	0.563	ambiguous	-0.128	Destabilizing	0.836	D	0.344	neutral	None	None	None	None	I
L/E	0.273	likely_benign	0.3037	benign	-0.212	Destabilizing	0.35	N	0.367	neutral	None	None	None	None	I
L/F	0.1338	likely_benign	0.1545	benign	-0.55	Destabilizing	0.757	D	0.331	neutral	N	0.512906439	None	None	I
L/G	0.4231	ambiguous	0.4789	ambiguous	-0.738	Destabilizing	0.422	N	0.378	neutral	None	None	None	None	I
L/H	0.2288	likely_benign	0.2531	benign	0.007	Stabilizing	0.004	N	0.363	neutral	None	None	None	None	I
L/I	0.0728	likely_benign	0.077	benign	-0.268	Destabilizing	0.041	N	0.359	neutral	None	None	None	None	I
L/K	0.2843	likely_benign	0.3044	benign	-0.347	Destabilizing	None	N	0.25	neutral	None	None	None	None	I
L/M	0.1067	likely_benign	0.1129	benign	-0.43	Destabilizing	0.74	D	0.345	neutral	N	0.491461276	None	None	I
L/N	0.2736	likely_benign	0.2921	benign	-0.186	Destabilizing	0.836	D	0.345	neutral	None	None	None	None	I
L/P	0.259	likely_benign	0.3367	benign	-0.338	Destabilizing	0.912	D	0.359	neutral	None	None	None	None	I
L/Q	0.1406	likely_benign	0.1538	benign	-0.383	Destabilizing	0.68	D	0.365	neutral	None	None	None	None	I
L/R	0.2404	likely_benign	0.2768	benign	0.186	Stabilizing	0.225	N	0.358	neutral	None	None	None	None	I
L/S	0.183	likely_benign	0.1948	benign	-0.639	Destabilizing	0.355	N	0.339	neutral	N	0.486867816	None	None	I
L/T	0.1667	likely_benign	0.1796	benign	-0.612	Destabilizing	0.305	N	0.334	neutral	None	None	None	None	I
L/V	0.0778	likely_benign	0.0853	benign	-0.338	Destabilizing	0.009	N	0.339	neutral	N	0.469495563	None	None	I
L/W	0.3307	likely_benign	0.3756	ambiguous	-0.57	Destabilizing	0.993	D	0.395	neutral	N	0.503071071	None	None	I
L/Y	0.3032	likely_benign	0.3401	ambiguous	-0.327	Destabilizing	0.193	N	0.329	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.