TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30202	90829;90830;90831	chr2:178552296;178552295;178552294	chr2:179417023;179417022;179417021
N2AB	28561	85906;85907;85908	chr2:178552296;178552295;178552294	chr2:179417023;179417022;179417021
N2A	27634	83125;83126;83127	chr2:178552296;178552295;178552294	chr2:179417023;179417022;179417021
N2B	21137	63634;63635;63636	chr2:178552296;178552295;178552294	chr2:179417023;179417022;179417021
Novex-1	21262	64009;64010;64011	chr2:178552296;178552295;178552294	chr2:179417023;179417022;179417021
Novex-2	21329	64210;64211;64212	chr2:178552296;178552295;178552294	chr2:179417023;179417022;179417021
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-148
• Domain position: 71
• Structural Position: 154
• Q(SASA): 0.1327
• 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
Y/H	rs1319107729	-2.251	1.0	D	0.785	0.86	0.76236827946	gnomAD-2.1.1	8.08E-06	None	None	None	None	N	None	0	0	None	0	5.58E-05	None	3.3E-05	None	0	0	0
Y/H	rs1319107729	-2.251	1.0	D	0.785	0.86	0.76236827946	gnomAD-4.0.0	4.79191E-06	None	None	None	None	N	None	0	0	None	0	2.52054E-05	None	0	0	8.99687E-07	5.81247E-05	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
Y/A	0.9986	likely_pathogenic	0.998	pathogenic	-2.592	Highly Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
Y/C	0.9782	likely_pathogenic	0.9704	pathogenic	-2.09	Highly Destabilizing	1.0	D	0.845	deleterious	D	0.634850224	None	None	N
Y/D	0.9985	likely_pathogenic	0.9979	pathogenic	-2.727	Highly Destabilizing	1.0	D	0.871	deleterious	D	0.634850224	None	None	N
Y/E	0.9994	likely_pathogenic	0.9991	pathogenic	-2.49	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
Y/F	0.3155	likely_benign	0.2709	benign	-0.945	Destabilizing	0.999	D	0.698	prob.neutral	D	0.587590434	None	None	N
Y/G	0.9961	likely_pathogenic	0.9946	pathogenic	-3.053	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
Y/H	0.9858	likely_pathogenic	0.9804	pathogenic	-2.025	Highly Destabilizing	1.0	D	0.785	deleterious	D	0.634648419	None	None	N
Y/I	0.9694	likely_pathogenic	0.9557	pathogenic	-1.077	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
Y/K	0.9994	likely_pathogenic	0.9992	pathogenic	-2.088	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
Y/L	0.9431	likely_pathogenic	0.9263	pathogenic	-1.077	Destabilizing	0.999	D	0.786	deleterious	None	None	None	None	N
Y/M	0.985	likely_pathogenic	0.9791	pathogenic	-1.159	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
Y/N	0.9901	likely_pathogenic	0.9854	pathogenic	-2.934	Highly Destabilizing	1.0	D	0.857	deleterious	D	0.634850224	None	None	N
Y/P	0.9996	likely_pathogenic	0.9994	pathogenic	-1.596	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
Y/Q	0.9993	likely_pathogenic	0.9989	pathogenic	-2.538	Highly Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
Y/R	0.9982	likely_pathogenic	0.9978	pathogenic	-2.131	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
Y/S	0.997	likely_pathogenic	0.9957	pathogenic	-3.397	Highly Destabilizing	1.0	D	0.869	deleterious	D	0.634850224	None	None	N
Y/T	0.9983	likely_pathogenic	0.9975	pathogenic	-3.015	Highly Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
Y/V	0.965	likely_pathogenic	0.9555	pathogenic	-1.596	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
Y/W	0.8924	likely_pathogenic	0.87	pathogenic	-0.297	Destabilizing	1.0	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.