TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34947	105064;105065;105066	chr2:178531776;178531775;178531774	chr2:179396503;179396502;179396501
N2AB	33306	100141;100142;100143	chr2:178531776;178531775;178531774	chr2:179396503;179396502;179396501
N2A	32379	97360;97361;97362	chr2:178531776;178531775;178531774	chr2:179396503;179396502;179396501
N2B	25882	77869;77870;77871	chr2:178531776;178531775;178531774	chr2:179396503;179396502;179396501
Novex-1	26007	78244;78245;78246	chr2:178531776;178531775;178531774	chr2:179396503;179396502;179396501
Novex-2	26074	78445;78446;78447	chr2:178531776;178531775;178531774	chr2:179396503;179396502;179396501
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-163
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.2879
• 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
R/K	None	None	0.997	N	0.562	0.246	0.422524665647	gnomAD-4.0.0	1.59089E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43275E-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
R/A	0.9763	likely_pathogenic	0.9701	pathogenic	-0.26	Destabilizing	0.999	D	0.645	neutral	None	None	None	None	I
R/C	0.8506	likely_pathogenic	0.8237	pathogenic	-0.276	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
R/D	0.9935	likely_pathogenic	0.9924	pathogenic	0.082	Stabilizing	1.0	D	0.746	deleterious	None	None	None	None	I
R/E	0.9622	likely_pathogenic	0.9565	pathogenic	0.209	Stabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	I
R/F	0.9845	likely_pathogenic	0.982	pathogenic	-0.125	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	I
R/G	0.9385	likely_pathogenic	0.9291	pathogenic	-0.561	Destabilizing	1.0	D	0.644	neutral	N	0.512894916	None	None	I
R/H	0.6165	likely_pathogenic	0.561	ambiguous	-1.027	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
R/I	0.9695	likely_pathogenic	0.9664	pathogenic	0.532	Stabilizing	1.0	D	0.761	deleterious	N	0.4806399	None	None	I
R/K	0.6106	likely_pathogenic	0.5658	pathogenic	-0.238	Destabilizing	0.997	D	0.562	neutral	N	0.484878808	None	None	I
R/L	0.9022	likely_pathogenic	0.8887	pathogenic	0.532	Stabilizing	1.0	D	0.644	neutral	None	None	None	None	I
R/M	0.9706	likely_pathogenic	0.9647	pathogenic	None	Stabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
R/N	0.9862	likely_pathogenic	0.9838	pathogenic	0.069	Stabilizing	1.0	D	0.766	deleterious	None	None	None	None	I
R/P	0.9552	likely_pathogenic	0.9535	pathogenic	0.291	Stabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
R/Q	0.6099	likely_pathogenic	0.5613	ambiguous	0.016	Stabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
R/S	0.9803	likely_pathogenic	0.9769	pathogenic	-0.477	Destabilizing	1.0	D	0.721	prob.delet.	N	0.514625712	None	None	I
R/T	0.9725	likely_pathogenic	0.9665	pathogenic	-0.168	Destabilizing	1.0	D	0.711	prob.delet.	N	0.490047649	None	None	I
R/V	0.9698	likely_pathogenic	0.9669	pathogenic	0.291	Stabilizing	1.0	D	0.756	deleterious	None	None	None	None	I
R/W	0.8412	likely_pathogenic	0.8288	pathogenic	0.034	Stabilizing	1.0	D	0.764	deleterious	None	None	None	None	I
R/Y	0.9628	likely_pathogenic	0.9567	pathogenic	0.377	Stabilizing	1.0	D	0.751	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.