TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17040	51343;51344;51345	chr2:178611011;178611010;178611009	chr2:179475738;179475737;179475736
N2AB	15399	46420;46421;46422	chr2:178611011;178611010;178611009	chr2:179475738;179475737;179475736
N2A	14472	43639;43640;43641	chr2:178611011;178611010;178611009	chr2:179475738;179475737;179475736
N2B	7975	24148;24149;24150	chr2:178611011;178611010;178611009	chr2:179475738;179475737;179475736
Novex-1	8100	24523;24524;24525	chr2:178611011;178611010;178611009	chr2:179475738;179475737;179475736
Novex-2	8167	24724;24725;24726	chr2:178611011;178611010;178611009	chr2:179475738;179475737;179475736
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-111
• Domain position: 86
• Structural Position: 172
• Q(SASA): 0.0613
• 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
I/M	rs1215488177	None	0.864	D	0.648	0.229	0.44389696681	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.94628E-04	None	0	0	0	0	0
I/M	rs1215488177	None	0.864	D	0.648	0.229	0.44389696681	gnomAD-4.0.0	6.57981E-06	None	None	None	None	N	None	0	0	None	0	1.94628E-04	None	0	0	0	0	0
I/V	rs727505039	-1.574	0.002	N	0.216	0.066	0.262175524916	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	1.16191E-04	None	0	0	None	0	None	0	0	0
I/V	rs727505039	-1.574	0.002	N	0.216	0.066	0.262175524916	gnomAD-4.0.0	4.79342E-06	None	None	None	None	N	None	0	1.11917E-04	None	0	0	None	0	0	9.00025E-07	0	1.65876E-05

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
I/A	0.7693	likely_pathogenic	0.7652	pathogenic	-2.561	Highly Destabilizing	0.547	D	0.651	neutral	None	None	None	None	N
I/C	0.7876	likely_pathogenic	0.7848	pathogenic	-2.125	Highly Destabilizing	0.985	D	0.733	prob.delet.	None	None	None	None	N
I/D	0.9928	likely_pathogenic	0.9907	pathogenic	-2.415	Highly Destabilizing	0.945	D	0.818	deleterious	None	None	None	None	N
I/E	0.9746	likely_pathogenic	0.9684	pathogenic	-2.194	Highly Destabilizing	0.945	D	0.819	deleterious	None	None	None	None	N
I/F	0.2813	likely_benign	0.2922	benign	-1.55	Destabilizing	0.864	D	0.679	prob.neutral	N	0.499765485	None	None	N
I/G	0.9595	likely_pathogenic	0.9573	pathogenic	-3.126	Highly Destabilizing	0.945	D	0.809	deleterious	None	None	None	None	N
I/H	0.9389	likely_pathogenic	0.9242	pathogenic	-2.507	Highly Destabilizing	0.995	D	0.797	deleterious	None	None	None	None	N
I/K	0.9226	likely_pathogenic	0.9022	pathogenic	-1.951	Destabilizing	0.945	D	0.817	deleterious	None	None	None	None	N
I/L	0.132	likely_benign	0.1421	benign	-0.935	Destabilizing	0.141	N	0.443	neutral	N	0.50675597	None	None	N
I/M	0.1543	likely_benign	0.1574	benign	-0.987	Destabilizing	0.864	D	0.648	neutral	D	0.670157903	None	None	N
I/N	0.9103	likely_pathogenic	0.8796	pathogenic	-2.238	Highly Destabilizing	0.975	D	0.821	deleterious	D	0.671555676	None	None	N
I/P	0.9903	likely_pathogenic	0.9909	pathogenic	-1.456	Destabilizing	0.981	D	0.814	deleterious	None	None	None	None	N
I/Q	0.9318	likely_pathogenic	0.9158	pathogenic	-2.092	Highly Destabilizing	0.981	D	0.827	deleterious	None	None	None	None	N
I/R	0.8852	likely_pathogenic	0.8595	pathogenic	-1.688	Destabilizing	0.945	D	0.825	deleterious	None	None	None	None	N
I/S	0.8888	likely_pathogenic	0.8668	pathogenic	-3.059	Highly Destabilizing	0.864	D	0.752	deleterious	D	0.541714218	None	None	N
I/T	0.786	likely_pathogenic	0.7563	pathogenic	-2.673	Highly Destabilizing	0.645	D	0.726	prob.delet.	N	0.512583378	None	None	N
I/V	0.0837	likely_benign	0.0755	benign	-1.456	Destabilizing	0.002	N	0.216	neutral	N	0.472691124	None	None	N
I/W	0.9189	likely_pathogenic	0.9243	pathogenic	-1.838	Destabilizing	0.995	D	0.779	deleterious	None	None	None	None	N
I/Y	0.783	likely_pathogenic	0.7698	pathogenic	-1.584	Destabilizing	0.945	D	0.746	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.