TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14768	44527;44528;44529	chr2:178629423;178629422;178629421	chr2:179494150;179494149;179494148
N2AB	13127	39604;39605;39606	chr2:178629423;178629422;178629421	chr2:179494150;179494149;179494148
N2A	12200	36823;36824;36825	chr2:178629423;178629422;178629421	chr2:179494150;179494149;179494148
N2B	5703	17332;17333;17334	chr2:178629423;178629422;178629421	chr2:179494150;179494149;179494148
Novex-1	5828	17707;17708;17709	chr2:178629423;178629422;178629421	chr2:179494150;179494149;179494148
Novex-2	5895	17908;17909;17910	chr2:178629423;178629422;178629421	chr2:179494150;179494149;179494148
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-99
• Domain position: 4
• Structural Position: 5
• Q(SASA): 0.5264
• 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
R/K	None	None	0.37	N	0.231	0.155	0.200317383148	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	6.17284E-04	0	0	3.66327E-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
R/A	0.726	likely_pathogenic	0.7935	pathogenic	-0.327	Destabilizing	0.983	D	0.588	neutral	None	None	None	None	N
R/C	0.3205	likely_benign	0.4486	ambiguous	-0.261	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
R/D	0.8948	likely_pathogenic	0.9313	pathogenic	0.032	Stabilizing	0.995	D	0.698	prob.neutral	None	None	None	None	N
R/E	0.6284	likely_pathogenic	0.6978	pathogenic	0.165	Stabilizing	0.967	D	0.54	neutral	None	None	None	None	N
R/F	0.7791	likely_pathogenic	0.8448	pathogenic	-0.103	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	N
R/G	0.5726	likely_pathogenic	0.6657	pathogenic	-0.647	Destabilizing	0.978	D	0.611	neutral	N	0.510398081	None	None	N
R/H	0.1426	likely_benign	0.2029	benign	-1.151	Destabilizing	0.999	D	0.662	neutral	None	None	None	None	N
R/I	0.5356	ambiguous	0.6385	pathogenic	0.524	Stabilizing	0.998	D	0.725	prob.delet.	None	None	None	None	N
R/K	0.1645	likely_benign	0.2202	benign	-0.39	Destabilizing	0.37	N	0.231	neutral	N	0.444037843	None	None	N
R/L	0.4341	ambiguous	0.5298	ambiguous	0.524	Stabilizing	0.983	D	0.611	neutral	None	None	None	None	N
R/M	0.5612	ambiguous	0.6971	pathogenic	0.028	Stabilizing	1.0	D	0.686	prob.neutral	D	0.579773377	None	None	N
R/N	0.7663	likely_pathogenic	0.8467	pathogenic	0.023	Stabilizing	0.995	D	0.619	neutral	None	None	None	None	N
R/P	0.9548	likely_pathogenic	0.9703	pathogenic	0.263	Stabilizing	0.998	D	0.728	prob.delet.	None	None	None	None	N
R/Q	0.1593	likely_benign	0.2062	benign	-0.031	Destabilizing	0.995	D	0.623	neutral	None	None	None	None	N
R/S	0.7507	likely_pathogenic	0.8268	pathogenic	-0.529	Destabilizing	0.978	D	0.657	neutral	N	0.50931781	None	None	N
R/T	0.5305	ambiguous	0.6607	pathogenic	-0.213	Destabilizing	0.997	D	0.672	neutral	N	0.506516677	None	None	N
R/V	0.6416	likely_pathogenic	0.7164	pathogenic	0.263	Stabilizing	0.998	D	0.721	prob.delet.	None	None	None	None	N
R/W	0.329	likely_benign	0.4309	ambiguous	0.107	Stabilizing	1.0	D	0.68	prob.neutral	D	0.555001522	None	None	N
R/Y	0.5964	likely_pathogenic	0.6957	pathogenic	0.42	Stabilizing	0.999	D	0.723	prob.delet.	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.