TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19245	57958;57959;57960	chr2:178595621;178595620;178595619	chr2:179460348;179460347;179460346
N2AB	17604	53035;53036;53037	chr2:178595621;178595620;178595619	chr2:179460348;179460347;179460346
N2A	16677	50254;50255;50256	chr2:178595621;178595620;178595619	chr2:179460348;179460347;179460346
N2B	10180	30763;30764;30765	chr2:178595621;178595620;178595619	chr2:179460348;179460347;179460346
Novex-1	10305	31138;31139;31140	chr2:178595621;178595620;178595619	chr2:179460348;179460347;179460346
Novex-2	10372	31339;31340;31341	chr2:178595621;178595620;178595619	chr2:179460348;179460347;179460346
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-27
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.1491
• 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	rs763810038	-0.267	0.603	N	0.543	0.215	0.551838628669	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	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
V/A	0.579	likely_pathogenic	0.6371	pathogenic	-1.821	Destabilizing	0.645	D	0.668	neutral	D	0.522354187	None	None	N
V/C	0.8918	likely_pathogenic	0.8981	pathogenic	-1.568	Destabilizing	0.995	D	0.737	prob.delet.	None	None	None	None	N
V/D	0.9937	likely_pathogenic	0.9949	pathogenic	-1.448	Destabilizing	0.006	N	0.694	prob.neutral	N	0.497749288	None	None	N
V/E	0.9778	likely_pathogenic	0.9814	pathogenic	-1.325	Destabilizing	0.547	D	0.768	deleterious	None	None	None	None	N
V/F	0.6051	likely_pathogenic	0.6298	pathogenic	-1.165	Destabilizing	0.975	D	0.733	prob.delet.	N	0.489934474	None	None	N
V/G	0.8917	likely_pathogenic	0.9054	pathogenic	-2.276	Highly Destabilizing	0.864	D	0.805	deleterious	D	0.523197377	None	None	N
V/H	0.9899	likely_pathogenic	0.9909	pathogenic	-1.715	Destabilizing	0.985	D	0.837	deleterious	None	None	None	None	N
V/I	0.0888	likely_benign	0.089	benign	-0.612	Destabilizing	0.603	D	0.543	neutral	N	0.507035231	None	None	N
V/K	0.9872	likely_pathogenic	0.9884	pathogenic	-1.502	Destabilizing	0.894	D	0.821	deleterious	None	None	None	None	N
V/L	0.48	ambiguous	0.4889	ambiguous	-0.612	Destabilizing	0.603	D	0.661	neutral	N	0.518113442	None	None	N
V/M	0.496	ambiguous	0.5513	ambiguous	-0.685	Destabilizing	0.981	D	0.715	prob.delet.	None	None	None	None	N
V/N	0.9801	likely_pathogenic	0.9826	pathogenic	-1.552	Destabilizing	0.809	D	0.851	deleterious	None	None	None	None	N
V/P	0.975	likely_pathogenic	0.9774	pathogenic	-0.982	Destabilizing	0.945	D	0.82	deleterious	None	None	None	None	N
V/Q	0.9741	likely_pathogenic	0.9769	pathogenic	-1.514	Destabilizing	0.894	D	0.821	deleterious	None	None	None	None	N
V/R	0.9769	likely_pathogenic	0.979	pathogenic	-1.183	Destabilizing	0.894	D	0.854	deleterious	None	None	None	None	N
V/S	0.8975	likely_pathogenic	0.9127	pathogenic	-2.256	Highly Destabilizing	0.809	D	0.798	deleterious	None	None	None	None	N
V/T	0.7939	likely_pathogenic	0.8107	pathogenic	-1.977	Destabilizing	0.707	D	0.65	neutral	None	None	None	None	N
V/W	0.9915	likely_pathogenic	0.9922	pathogenic	-1.4	Destabilizing	0.995	D	0.802	deleterious	None	None	None	None	N
V/Y	0.9595	likely_pathogenic	0.9657	pathogenic	-1.085	Destabilizing	0.981	D	0.73	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.