TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31941	96046;96047;96048	chr2:178544408;178544407;178544406	chr2:179409135;179409134;179409133
N2AB	30300	91123;91124;91125	chr2:178544408;178544407;178544406	chr2:179409135;179409134;179409133
N2A	29373	88342;88343;88344	chr2:178544408;178544407;178544406	chr2:179409135;179409134;179409133
N2B	22876	68851;68852;68853	chr2:178544408;178544407;178544406	chr2:179409135;179409134;179409133
Novex-1	23001	69226;69227;69228	chr2:178544408;178544407;178544406	chr2:179409135;179409134;179409133
Novex-2	23068	69427;69428;69429	chr2:178544408;178544407;178544406	chr2:179409135;179409134;179409133
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-121
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.1678
• 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
I/S	rs779376834	-2.402	0.966	N	0.753	0.518	0.846433868311	gnomAD-2.1.1	8.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
I/S	rs779376834	-2.402	0.966	N	0.753	0.518	0.846433868311	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/S	rs779376834	-2.402	0.966	N	0.753	0.518	0.846433868311	gnomAD-4.0.0	9.2961E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.27152E-05	0	0
I/T	rs779376834	-2.144	0.801	N	0.693	0.484	0.777538414374	gnomAD-2.1.1	3.18E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
I/T	rs779376834	-2.144	0.801	N	0.693	0.484	0.777538414374	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	4.41E-05	0	0
I/T	rs779376834	-2.144	0.801	N	0.693	0.484	0.777538414374	gnomAD-4.0.0	2.47896E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.39072E-06	0	0
I/V	rs750955565	-1.409	0.007	N	0.153	0.097	0.457286136841	gnomAD-2.1.1	8.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
I/V	rs750955565	-1.409	0.007	N	0.153	0.097	0.457286136841	gnomAD-4.0.0	3.18281E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.71772E-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
I/A	0.5844	likely_pathogenic	0.5461	ambiguous	-2.147	Highly Destabilizing	0.688	D	0.585	neutral	None	None	None	None	I
I/C	0.8592	likely_pathogenic	0.8416	pathogenic	-1.389	Destabilizing	0.998	D	0.665	neutral	None	None	None	None	I
I/D	0.9731	likely_pathogenic	0.9631	pathogenic	-1.682	Destabilizing	0.991	D	0.775	deleterious	None	None	None	None	I
I/E	0.9531	likely_pathogenic	0.9377	pathogenic	-1.6	Destabilizing	0.991	D	0.785	deleterious	None	None	None	None	I
I/F	0.591	likely_pathogenic	0.5636	ambiguous	-1.402	Destabilizing	0.934	D	0.671	neutral	N	0.519105546	None	None	I
I/G	0.9303	likely_pathogenic	0.9169	pathogenic	-2.568	Highly Destabilizing	0.991	D	0.797	deleterious	None	None	None	None	I
I/H	0.9463	likely_pathogenic	0.933	pathogenic	-1.767	Destabilizing	0.998	D	0.745	deleterious	None	None	None	None	I
I/K	0.9202	likely_pathogenic	0.8979	pathogenic	-1.541	Destabilizing	0.974	D	0.791	deleterious	None	None	None	None	I
I/L	0.18	likely_benign	0.173	benign	-1.011	Destabilizing	0.005	N	0.173	neutral	N	0.506152584	None	None	I
I/M	0.2282	likely_benign	0.2113	benign	-0.803	Destabilizing	0.934	D	0.653	neutral	N	0.521640441	None	None	I
I/N	0.7843	likely_pathogenic	0.7345	pathogenic	-1.478	Destabilizing	0.989	D	0.782	deleterious	N	0.514260609	None	None	I
I/P	0.8076	likely_pathogenic	0.8258	pathogenic	-1.362	Destabilizing	0.991	D	0.781	deleterious	None	None	None	None	I
I/Q	0.9353	likely_pathogenic	0.9172	pathogenic	-1.564	Destabilizing	0.991	D	0.779	deleterious	None	None	None	None	I
I/R	0.8874	likely_pathogenic	0.8498	pathogenic	-0.994	Destabilizing	0.974	D	0.78	deleterious	None	None	None	None	I
I/S	0.7413	likely_pathogenic	0.6854	pathogenic	-2.189	Highly Destabilizing	0.966	D	0.753	deleterious	N	0.510373042	None	None	I
I/T	0.3595	ambiguous	0.2864	benign	-1.976	Destabilizing	0.801	D	0.693	prob.neutral	N	0.510373041	None	None	I
I/V	0.0755	likely_benign	0.0692	benign	-1.362	Destabilizing	0.007	N	0.153	neutral	N	0.473232089	None	None	I
I/W	0.9801	likely_pathogenic	0.9757	pathogenic	-1.55	Destabilizing	0.998	D	0.768	deleterious	None	None	None	None	I
I/Y	0.9195	likely_pathogenic	0.9035	pathogenic	-1.326	Destabilizing	0.974	D	0.695	prob.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.