TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16966	51121;51122;51123	chr2:178611233;178611232;178611231	chr2:179475960;179475959;179475958
N2AB	15325	46198;46199;46200	chr2:178611233;178611232;178611231	chr2:179475960;179475959;179475958
N2A	14398	43417;43418;43419	chr2:178611233;178611232;178611231	chr2:179475960;179475959;179475958
N2B	7901	23926;23927;23928	chr2:178611233;178611232;178611231	chr2:179475960;179475959;179475958
Novex-1	8026	24301;24302;24303	chr2:178611233;178611232;178611231	chr2:179475960;179475959;179475958
Novex-2	8093	24502;24503;24504	chr2:178611233;178611232;178611231	chr2:179475960;179475959;179475958
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-111
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.2101
• 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/G	None	None	1.0	D	0.721	0.796	0.899195765859	gnomAD-4.0.0	1.59394E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43377E-05	0
V/I	None	None	0.997	N	0.481	0.402	0.798506520085	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
V/A	0.4653	ambiguous	0.482	ambiguous	-1.69	Destabilizing	0.999	D	0.463	neutral	N	0.514133588	None	None	I
V/C	0.8644	likely_pathogenic	0.8538	pathogenic	-1.333	Destabilizing	1.0	D	0.627	neutral	None	None	None	None	I
V/D	0.9557	likely_pathogenic	0.9628	pathogenic	-1.623	Destabilizing	1.0	D	0.732	prob.delet.	D	0.749971047	None	None	I
V/E	0.9015	likely_pathogenic	0.9114	pathogenic	-1.518	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
V/F	0.5475	ambiguous	0.5935	pathogenic	-1.07	Destabilizing	1.0	D	0.729	prob.delet.	D	0.640951556	None	None	I
V/G	0.6785	likely_pathogenic	0.6985	pathogenic	-2.11	Highly Destabilizing	1.0	D	0.721	prob.delet.	D	0.650841267	None	None	I
V/H	0.9477	likely_pathogenic	0.9529	pathogenic	-1.699	Destabilizing	1.0	D	0.648	neutral	None	None	None	None	I
V/I	0.0977	likely_benign	0.1002	benign	-0.587	Destabilizing	0.997	D	0.481	neutral	N	0.516673248	None	None	I
V/K	0.8825	likely_pathogenic	0.8967	pathogenic	-1.355	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
V/L	0.3991	ambiguous	0.435	ambiguous	-0.587	Destabilizing	0.997	D	0.49	neutral	D	0.523186421	None	None	I
V/M	0.3895	ambiguous	0.4302	ambiguous	-0.65	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
V/N	0.876	likely_pathogenic	0.8956	pathogenic	-1.372	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	I
V/P	0.9786	likely_pathogenic	0.9768	pathogenic	-0.922	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
V/Q	0.8524	likely_pathogenic	0.8674	pathogenic	-1.389	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
V/R	0.8492	likely_pathogenic	0.8584	pathogenic	-1.036	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
V/S	0.7121	likely_pathogenic	0.7362	pathogenic	-2.005	Highly Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	I
V/T	0.5099	ambiguous	0.5247	ambiguous	-1.774	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	I
V/W	0.9857	likely_pathogenic	0.9873	pathogenic	-1.384	Destabilizing	1.0	D	0.616	neutral	None	None	None	None	I
V/Y	0.9295	likely_pathogenic	0.9392	pathogenic	-1.034	Destabilizing	1.0	D	0.73	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.