TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20301	61126;61127;61128	chr2:178590824;178590823;178590822	chr2:179455551;179455550;179455549
N2AB	18660	56203;56204;56205	chr2:178590824;178590823;178590822	chr2:179455551;179455550;179455549
N2A	17733	53422;53423;53424	chr2:178590824;178590823;178590822	chr2:179455551;179455550;179455549
N2B	11236	33931;33932;33933	chr2:178590824;178590823;178590822	chr2:179455551;179455550;179455549
Novex-1	11361	34306;34307;34308	chr2:178590824;178590823;178590822	chr2:179455551;179455550;179455549
Novex-2	11428	34507;34508;34509	chr2:178590824;178590823;178590822	chr2:179455551;179455550;179455549
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-35
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.2413
• 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
S/G	None	None	0.939	N	0.603	0.28	0.225215365344	gnomAD-4.0.0	1.60873E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.90458E-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
S/A	0.2438	likely_benign	0.2462	benign	-0.485	Destabilizing	0.807	D	0.589	neutral	None	None	None	None	I
S/C	0.1731	likely_benign	0.1856	benign	-0.31	Destabilizing	0.999	D	0.656	neutral	N	0.479121147	None	None	I
S/D	0.8989	likely_pathogenic	0.9004	pathogenic	-0.217	Destabilizing	0.953	D	0.7	prob.neutral	None	None	None	None	I
S/E	0.9287	likely_pathogenic	0.939	pathogenic	-0.287	Destabilizing	0.953	D	0.689	prob.neutral	None	None	None	None	I
S/F	0.5229	ambiguous	0.6024	pathogenic	-0.951	Destabilizing	0.993	D	0.72	prob.delet.	None	None	None	None	I
S/G	0.4237	ambiguous	0.4331	ambiguous	-0.646	Destabilizing	0.939	D	0.603	neutral	N	0.471476781	None	None	I
S/H	0.6231	likely_pathogenic	0.6596	pathogenic	-1.236	Destabilizing	0.999	D	0.649	neutral	None	None	None	None	I
S/I	0.6099	likely_pathogenic	0.6306	pathogenic	-0.182	Destabilizing	0.982	D	0.73	prob.delet.	N	0.50336424	None	None	I
S/K	0.9588	likely_pathogenic	0.9725	pathogenic	-0.619	Destabilizing	0.953	D	0.698	prob.neutral	None	None	None	None	I
S/L	0.2157	likely_benign	0.258	benign	-0.182	Destabilizing	0.91	D	0.686	prob.neutral	None	None	None	None	I
S/M	0.3888	ambiguous	0.4534	ambiguous	0.218	Stabilizing	0.999	D	0.649	neutral	None	None	None	None	I
S/N	0.4058	ambiguous	0.4002	ambiguous	-0.405	Destabilizing	0.939	D	0.707	prob.neutral	N	0.50056631	None	None	I
S/P	0.9891	likely_pathogenic	0.9892	pathogenic	-0.252	Destabilizing	0.993	D	0.669	neutral	None	None	None	None	I
S/Q	0.8394	likely_pathogenic	0.8653	pathogenic	-0.69	Destabilizing	0.993	D	0.716	prob.delet.	None	None	None	None	I
S/R	0.944	likely_pathogenic	0.9574	pathogenic	-0.406	Destabilizing	0.991	D	0.668	neutral	N	0.491461276	None	None	I
S/T	0.2521	likely_benign	0.2799	benign	-0.465	Destabilizing	0.17	N	0.5	neutral	N	0.484512743	None	None	I
S/V	0.5605	ambiguous	0.5754	pathogenic	-0.252	Destabilizing	0.973	D	0.699	prob.neutral	None	None	None	None	I
S/W	0.7207	likely_pathogenic	0.7791	pathogenic	-0.926	Destabilizing	0.999	D	0.78	deleterious	None	None	None	None	I
S/Y	0.4475	ambiguous	0.5202	ambiguous	-0.66	Destabilizing	0.998	D	0.72	prob.delet.	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.