TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30694	92305;92306;92307	chr2:178549642;178549641;178549640	chr2:179414369;179414368;179414367
N2AB	29053	87382;87383;87384	chr2:178549642;178549641;178549640	chr2:179414369;179414368;179414367
N2A	28126	84601;84602;84603	chr2:178549642;178549641;178549640	chr2:179414369;179414368;179414367
N2B	21629	65110;65111;65112	chr2:178549642;178549641;178549640	chr2:179414369;179414368;179414367
Novex-1	21754	65485;65486;65487	chr2:178549642;178549641;178549640	chr2:179414369;179414368;179414367
Novex-2	21821	65686;65687;65688	chr2:178549642;178549641;178549640	chr2:179414369;179414368;179414367
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-111
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.0881
• 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
V/I	rs1301174075	-0.891	None	D	0.185	0.191	0.440288351245	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	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
V/A	0.8767	likely_pathogenic	0.8884	pathogenic	-2.508	Highly Destabilizing	0.104	N	0.545	neutral	D	0.569102439	None	None	N
V/C	0.9487	likely_pathogenic	0.946	pathogenic	-2.012	Highly Destabilizing	0.968	D	0.745	deleterious	None	None	None	None	N
V/D	0.998	likely_pathogenic	0.9981	pathogenic	-3.571	Highly Destabilizing	0.667	D	0.874	deleterious	D	0.647592509	None	None	N
V/E	0.9933	likely_pathogenic	0.9936	pathogenic	-3.258	Highly Destabilizing	0.726	D	0.837	deleterious	None	None	None	None	N
V/F	0.7472	likely_pathogenic	0.8067	pathogenic	-1.437	Destabilizing	0.497	N	0.721	prob.delet.	D	0.580458744	None	None	N
V/G	0.955	likely_pathogenic	0.9606	pathogenic	-3.098	Highly Destabilizing	0.667	D	0.856	deleterious	D	0.647592509	None	None	N
V/H	0.9968	likely_pathogenic	0.9974	pathogenic	-2.981	Highly Destabilizing	0.968	D	0.878	deleterious	None	None	None	None	N
V/I	0.0684	likely_benign	0.0695	benign	-0.783	Destabilizing	None	N	0.185	neutral	D	0.52988874	None	None	N
V/K	0.9925	likely_pathogenic	0.9939	pathogenic	-2.169	Highly Destabilizing	0.726	D	0.838	deleterious	None	None	None	None	N
V/L	0.4292	ambiguous	0.4319	ambiguous	-0.783	Destabilizing	0.009	N	0.281	neutral	D	0.531800611	None	None	N
V/M	0.5816	likely_pathogenic	0.6223	pathogenic	-1.053	Destabilizing	0.567	D	0.613	neutral	None	None	None	None	N
V/N	0.9909	likely_pathogenic	0.9919	pathogenic	-2.836	Highly Destabilizing	0.89	D	0.886	deleterious	None	None	None	None	N
V/P	0.9933	likely_pathogenic	0.9938	pathogenic	-1.341	Destabilizing	0.89	D	0.851	deleterious	None	None	None	None	N
V/Q	0.9911	likely_pathogenic	0.9923	pathogenic	-2.497	Highly Destabilizing	0.89	D	0.869	deleterious	None	None	None	None	N
V/R	0.9872	likely_pathogenic	0.9897	pathogenic	-2.188	Highly Destabilizing	0.726	D	0.881	deleterious	None	None	None	None	N
V/S	0.9751	likely_pathogenic	0.9769	pathogenic	-3.326	Highly Destabilizing	0.726	D	0.8	deleterious	None	None	None	None	N
V/T	0.9314	likely_pathogenic	0.9343	pathogenic	-2.863	Highly Destabilizing	0.272	N	0.58	neutral	None	None	None	None	N
V/W	0.996	likely_pathogenic	0.9972	pathogenic	-2.039	Highly Destabilizing	0.968	D	0.857	deleterious	None	None	None	None	N
V/Y	0.9788	likely_pathogenic	0.9838	pathogenic	-1.738	Destabilizing	0.726	D	0.724	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.