TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24668	74227;74228;74229	chr2:178572130;178572129;178572128	chr2:179436857;179436856;179436855
N2AB	23027	69304;69305;69306	chr2:178572130;178572129;178572128	chr2:179436857;179436856;179436855
N2A	22100	66523;66524;66525	chr2:178572130;178572129;178572128	chr2:179436857;179436856;179436855
N2B	15603	47032;47033;47034	chr2:178572130;178572129;178572128	chr2:179436857;179436856;179436855
Novex-1	15728	47407;47408;47409	chr2:178572130;178572129;178572128	chr2:179436857;179436856;179436855
Novex-2	15795	47608;47609;47610	chr2:178572130;178572129;178572128	chr2:179436857;179436856;179436855
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-67
• Domain position: 53
• Structural Position: 70
• Q(SASA): 0.4023
• 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
T/I	rs771515164	0.199	0.665	N	0.609	0.184	0.294918367191	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
T/I	rs771515164	0.199	0.665	N	0.609	0.184	0.294918367191	gnomAD-4.0.0	6.84429E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99624E-07	0	0
T/R	None	None	0.949	N	0.701	0.356	0.355034743287	gnomAD-4.0.0	6.84429E-07	None	None	None	None	I	None	0	0	None	0	2.52845E-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
T/A	0.078	likely_benign	0.0758	benign	-0.302	Destabilizing	0.054	N	0.492	neutral	N	0.517670725	None	None	I
T/C	0.3731	ambiguous	0.3831	ambiguous	-0.303	Destabilizing	0.997	D	0.701	prob.neutral	None	None	None	None	I
T/D	0.4542	ambiguous	0.4455	ambiguous	0.331	Stabilizing	0.798	D	0.682	prob.neutral	None	None	None	None	I
T/E	0.3257	likely_benign	0.3215	benign	0.268	Stabilizing	0.653	D	0.632	neutral	None	None	None	None	I
T/F	0.2315	likely_benign	0.2171	benign	-0.735	Destabilizing	0.99	D	0.791	deleterious	None	None	None	None	I
T/G	0.2875	likely_benign	0.2805	benign	-0.45	Destabilizing	0.904	D	0.681	prob.neutral	None	None	None	None	I
T/H	0.2081	likely_benign	0.2195	benign	-0.742	Destabilizing	0.993	D	0.777	deleterious	None	None	None	None	I
T/I	0.1285	likely_benign	0.1182	benign	-0.034	Destabilizing	0.665	D	0.609	neutral	N	0.464212307	None	None	I
T/K	0.1908	likely_benign	0.1905	benign	-0.314	Destabilizing	0.028	N	0.337	neutral	N	0.484753017	None	None	I
T/L	0.0905	likely_benign	0.0863	benign	-0.034	Destabilizing	0.724	D	0.599	neutral	None	None	None	None	I
T/M	0.0812	likely_benign	0.0786	benign	0.02	Stabilizing	0.974	D	0.72	prob.delet.	None	None	None	None	I
T/N	0.109	likely_benign	0.1119	benign	-0.15	Destabilizing	0.798	D	0.577	neutral	None	None	None	None	I
T/P	0.2612	likely_benign	0.2398	benign	-0.093	Destabilizing	0.858	D	0.717	prob.delet.	N	0.480963351	None	None	I
T/Q	0.1868	likely_benign	0.1947	benign	-0.337	Destabilizing	0.896	D	0.725	prob.delet.	None	None	None	None	I
T/R	0.1633	likely_benign	0.1615	benign	-0.095	Destabilizing	0.949	D	0.701	prob.neutral	N	0.46591654	None	None	I
T/S	0.1031	likely_benign	0.1045	benign	-0.374	Destabilizing	0.216	N	0.486	neutral	N	0.474074664	None	None	I
T/V	0.0924	likely_benign	0.0875	benign	-0.093	Destabilizing	0.048	N	0.219	neutral	None	None	None	None	I
T/W	0.5827	likely_pathogenic	0.5831	pathogenic	-0.747	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	I
T/Y	0.2622	likely_benign	0.2692	benign	-0.453	Destabilizing	0.997	D	0.793	deleterious	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.