TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35308	106147;106148;106149	chr2:178530693;178530692;178530691	chr2:179395420;179395419;179395418
N2AB	33667	101224;101225;101226	chr2:178530693;178530692;178530691	chr2:179395420;179395419;179395418
N2A	32740	98443;98444;98445	chr2:178530693;178530692;178530691	chr2:179395420;179395419;179395418
N2B	26243	78952;78953;78954	chr2:178530693;178530692;178530691	chr2:179395420;179395419;179395418
Novex-1	26368	79327;79328;79329	chr2:178530693;178530692;178530691	chr2:179395420;179395419;179395418
Novex-2	26435	79528;79529;79530	chr2:178530693;178530692;178530691	chr2:179395420;179395419;179395418
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-165
• Domain position: 23
• Structural Position: 36
• Q(SASA): 0.2698
• 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
E/A	rs754935594	-0.836	0.089	N	0.559	0.161	0.191931220699	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	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
E/A	0.1889	likely_benign	0.2121	benign	-0.655	Destabilizing	0.089	N	0.559	neutral	N	0.445692331	None	None	N
E/C	0.9118	likely_pathogenic	0.9253	pathogenic	-0.035	Destabilizing	0.955	D	0.722	prob.delet.	None	None	None	None	N
E/D	0.116	likely_benign	0.1412	benign	-0.525	Destabilizing	0.001	N	0.264	neutral	N	0.45296502	None	None	N
E/F	0.8336	likely_pathogenic	0.8573	pathogenic	-0.547	Destabilizing	0.955	D	0.76	deleterious	None	None	None	None	N
E/G	0.1786	likely_benign	0.1975	benign	-0.877	Destabilizing	0.163	N	0.643	neutral	N	0.491099334	None	None	N
E/H	0.5601	ambiguous	0.6132	pathogenic	-0.532	Destabilizing	0.774	D	0.588	neutral	None	None	None	None	N
E/I	0.5874	likely_pathogenic	0.6186	pathogenic	-0.094	Destabilizing	0.648	D	0.783	deleterious	None	None	None	None	N
E/K	0.2053	likely_benign	0.2265	benign	0.23	Stabilizing	0.089	N	0.427	neutral	N	0.465816887	None	None	N
E/L	0.5845	likely_pathogenic	0.6393	pathogenic	-0.094	Destabilizing	0.476	N	0.763	deleterious	None	None	None	None	N
E/M	0.6494	likely_pathogenic	0.6887	pathogenic	0.203	Stabilizing	0.874	D	0.739	prob.delet.	None	None	None	None	N
E/N	0.2668	likely_benign	0.3093	benign	-0.145	Destabilizing	0.313	N	0.573	neutral	None	None	None	None	N
E/P	0.6326	likely_pathogenic	0.7248	pathogenic	-0.261	Destabilizing	0.648	D	0.741	deleterious	None	None	None	None	N
E/Q	0.184	likely_benign	0.2055	benign	-0.112	Destabilizing	0.001	N	0.204	neutral	N	0.448289919	None	None	N
E/R	0.3508	ambiguous	0.3859	ambiguous	0.339	Stabilizing	0.313	N	0.569	neutral	None	None	None	None	N
E/S	0.2139	likely_benign	0.242	benign	-0.302	Destabilizing	0.115	N	0.472	neutral	None	None	None	None	N
E/T	0.2955	likely_benign	0.3353	benign	-0.117	Destabilizing	0.476	N	0.706	prob.neutral	None	None	None	None	N
E/V	0.3753	ambiguous	0.4085	ambiguous	-0.261	Destabilizing	0.407	N	0.744	deleterious	N	0.477129959	None	None	N
E/W	0.9366	likely_pathogenic	0.9473	pathogenic	-0.356	Destabilizing	0.955	D	0.719	prob.delet.	None	None	None	None	N
E/Y	0.7352	likely_pathogenic	0.7689	pathogenic	-0.292	Destabilizing	0.648	D	0.755	deleterious	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.