TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1100	3523;3524;3525	chr2:178782294;178782293;178782292	chr2:179647021;179647020;179647019
N2AB	1100	3523;3524;3525	chr2:178782294;178782293;178782292	chr2:179647021;179647020;179647019
N2A	1100	3523;3524;3525	chr2:178782294;178782293;178782292	chr2:179647021;179647020;179647019
N2B	1054	3385;3386;3387	chr2:178782294;178782293;178782292	chr2:179647021;179647020;179647019
Novex-1	1054	3385;3386;3387	chr2:178782294;178782293;178782292	chr2:179647021;179647020;179647019
Novex-2	1054	3385;3386;3387	chr2:178782294;178782293;178782292	chr2:179647021;179647020;179647019
Novex-3	1100	3523;3524;3525	chr2:178782294;178782293;178782292	chr2:179647021;179647020;179647019

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-4
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.5174
• 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
V/M	None	None	0.942	N	0.605	0.17	0.407767136052	gnomAD-4.0.0	1.59051E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02151E-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
V/A	0.2359	likely_benign	0.2431	benign	-1.013	Destabilizing	0.014	N	0.433	neutral	N	0.455470157	None	None	I
V/C	0.821	likely_pathogenic	0.8049	pathogenic	-0.872	Destabilizing	0.994	D	0.647	neutral	None	None	None	None	I
V/D	0.4648	ambiguous	0.449	ambiguous	-0.511	Destabilizing	0.978	D	0.691	prob.neutral	None	None	None	None	I
V/E	0.3	likely_benign	0.2925	benign	-0.478	Destabilizing	0.942	D	0.68	prob.neutral	N	0.45020853	None	None	I
V/F	0.2151	likely_benign	0.2137	benign	-0.596	Destabilizing	0.043	N	0.421	neutral	None	None	None	None	I
V/G	0.3944	ambiguous	0.3877	ambiguous	-1.328	Destabilizing	0.89	D	0.653	neutral	D	0.575139584	None	None	I
V/H	0.6685	likely_pathogenic	0.6595	pathogenic	-0.646	Destabilizing	0.998	D	0.675	neutral	None	None	None	None	I
V/I	0.0824	likely_benign	0.087	benign	-0.253	Destabilizing	0.019	N	0.407	neutral	None	None	None	None	I
V/K	0.6268	likely_pathogenic	0.6085	pathogenic	-0.847	Destabilizing	0.956	D	0.683	prob.neutral	None	None	None	None	I
V/L	0.2265	likely_benign	0.2395	benign	-0.253	Destabilizing	0.489	N	0.545	neutral	N	0.440041304	None	None	I
V/M	0.1644	likely_benign	0.1746	benign	-0.429	Destabilizing	0.942	D	0.605	neutral	N	0.450393571	None	None	I
V/N	0.358	ambiguous	0.3643	ambiguous	-0.812	Destabilizing	0.978	D	0.689	prob.neutral	None	None	None	None	I
V/P	0.9508	likely_pathogenic	0.9497	pathogenic	-0.471	Destabilizing	0.978	D	0.677	prob.neutral	None	None	None	None	I
V/Q	0.4252	ambiguous	0.4163	ambiguous	-0.865	Destabilizing	0.978	D	0.681	prob.neutral	None	None	None	None	I
V/R	0.5527	ambiguous	0.5286	ambiguous	-0.443	Destabilizing	0.978	D	0.69	prob.neutral	None	None	None	None	I
V/S	0.2274	likely_benign	0.2325	benign	-1.371	Destabilizing	0.915	D	0.636	neutral	None	None	None	None	I
V/T	0.1751	likely_benign	0.1846	benign	-1.209	Destabilizing	0.86	D	0.527	neutral	None	None	None	None	I
V/W	0.8864	likely_pathogenic	0.8819	pathogenic	-0.778	Destabilizing	0.998	D	0.685	prob.neutral	None	None	None	None	I
V/Y	0.6356	likely_pathogenic	0.6292	pathogenic	-0.457	Destabilizing	0.915	D	0.665	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.