TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24735	74428;74429;74430	chr2:178571929;178571928;178571927	chr2:179436656;179436655;179436654
N2AB	23094	69505;69506;69507	chr2:178571929;178571928;178571927	chr2:179436656;179436655;179436654
N2A	22167	66724;66725;66726	chr2:178571929;178571928;178571927	chr2:179436656;179436655;179436654
N2B	15670	47233;47234;47235	chr2:178571929;178571928;178571927	chr2:179436656;179436655;179436654
Novex-1	15795	47608;47609;47610	chr2:178571929;178571928;178571927	chr2:179436656;179436655;179436654
Novex-2	15862	47809;47810;47811	chr2:178571929;178571928;178571927	chr2:179436656;179436655;179436654
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: Ig-133
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.0693
• 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/A	rs993249767	None	0.104	N	0.629	0.331	0.459192005304	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.93498E-04	None	0	0	0	0	0
V/A	rs993249767	None	0.104	N	0.629	0.331	0.459192005304	gnomAD-4.0.0	1.23985E-06	None	None	None	None	N	None	0	0	None	0	4.47167E-05	None	0	0	0	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	0.5065	ambiguous	0.5166	ambiguous	-1.51	Destabilizing	0.104	N	0.629	neutral	N	0.517916733	None	None	N
V/C	0.8772	likely_pathogenic	0.8901	pathogenic	-1.09	Destabilizing	0.968	D	0.779	deleterious	None	None	None	None	N
V/D	0.9866	likely_pathogenic	0.9917	pathogenic	-1.509	Destabilizing	0.667	D	0.878	deleterious	N	0.501114466	None	None	N
V/E	0.9712	likely_pathogenic	0.977	pathogenic	-1.28	Destabilizing	0.726	D	0.83	deleterious	None	None	None	None	N
V/F	0.4318	ambiguous	0.4786	ambiguous	-0.867	Destabilizing	0.497	N	0.766	deleterious	N	0.441906317	None	None	N
V/G	0.8	likely_pathogenic	0.8229	pathogenic	-2.01	Highly Destabilizing	0.667	D	0.854	deleterious	N	0.501114466	None	None	N
V/H	0.9869	likely_pathogenic	0.9902	pathogenic	-1.577	Destabilizing	0.968	D	0.869	deleterious	None	None	None	None	N
V/I	0.0667	likely_benign	0.0741	benign	-0.125	Destabilizing	None	N	0.195	neutral	N	0.388411054	None	None	N
V/K	0.9768	likely_pathogenic	0.9811	pathogenic	-1.131	Destabilizing	0.726	D	0.833	deleterious	None	None	None	None	N
V/L	0.244	likely_benign	0.2912	benign	-0.125	Destabilizing	None	N	0.304	neutral	N	0.363386818	None	None	N
V/M	0.2823	likely_benign	0.3217	benign	-0.273	Destabilizing	0.567	D	0.655	neutral	None	None	None	None	N
V/N	0.9652	likely_pathogenic	0.9776	pathogenic	-1.541	Destabilizing	0.89	D	0.873	deleterious	None	None	None	None	N
V/P	0.9678	likely_pathogenic	0.9755	pathogenic	-0.56	Destabilizing	0.89	D	0.853	deleterious	None	None	None	None	N
V/Q	0.9686	likely_pathogenic	0.9728	pathogenic	-1.29	Destabilizing	0.89	D	0.863	deleterious	None	None	None	None	N
V/R	0.9611	likely_pathogenic	0.968	pathogenic	-1.178	Destabilizing	0.726	D	0.874	deleterious	None	None	None	None	N
V/S	0.883	likely_pathogenic	0.9082	pathogenic	-2.185	Highly Destabilizing	0.726	D	0.813	deleterious	None	None	None	None	N
V/T	0.7054	likely_pathogenic	0.7289	pathogenic	-1.788	Destabilizing	0.272	N	0.649	neutral	None	None	None	None	N
V/W	0.9639	likely_pathogenic	0.9713	pathogenic	-1.226	Destabilizing	0.968	D	0.853	deleterious	None	None	None	None	N
V/Y	0.9037	likely_pathogenic	0.9216	pathogenic	-0.818	Destabilizing	0.726	D	0.777	deleterious	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.