TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23252	69979;69980;69981	chr2:178576378;178576377;178576376	chr2:179441105;179441104;179441103
N2AB	21611	65056;65057;65058	chr2:178576378;178576377;178576376	chr2:179441105;179441104;179441103
N2A	20684	62275;62276;62277	chr2:178576378;178576377;178576376	chr2:179441105;179441104;179441103
N2B	14187	42784;42785;42786	chr2:178576378;178576377;178576376	chr2:179441105;179441104;179441103
Novex-1	14312	43159;43160;43161	chr2:178576378;178576377;178576376	chr2:179441105;179441104;179441103
Novex-2	14379	43360;43361;43362	chr2:178576378;178576377;178576376	chr2:179441105;179441104;179441103
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-57
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.4011
• 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
T/I	None	None	1.0	N	0.78	0.426	0.344251166708	gnomAD-4.0.0	7.10046E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.15186E-07	0	0
T/S	rs1710103271	None	0.999	N	0.476	0.358	0.192905019026	gnomAD-4.0.0	7.10046E-07	None	None	None	None	N	None	3.24781E-05	0	None	0	0	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	0.2647	likely_benign	0.2741	benign	-0.8	Destabilizing	0.999	D	0.5	neutral	N	0.486118454	None	None	N
T/C	0.602	likely_pathogenic	0.5919	pathogenic	-0.868	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
T/D	0.9107	likely_pathogenic	0.9054	pathogenic	-1.256	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
T/E	0.8301	likely_pathogenic	0.8276	pathogenic	-1.253	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
T/F	0.5249	ambiguous	0.4943	ambiguous	-1.208	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
T/G	0.7086	likely_pathogenic	0.6972	pathogenic	-0.995	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
T/H	0.5779	likely_pathogenic	0.5625	ambiguous	-1.397	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
T/I	0.3047	likely_benign	0.2901	benign	-0.372	Destabilizing	1.0	D	0.78	deleterious	N	0.460795935	None	None	N
T/K	0.5075	ambiguous	0.4998	ambiguous	-0.667	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
T/L	0.2431	likely_benign	0.2297	benign	-0.372	Destabilizing	0.999	D	0.684	prob.neutral	None	None	None	None	N
T/M	0.1464	likely_benign	0.1434	benign	-0.017	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
T/N	0.4783	ambiguous	0.4846	ambiguous	-0.828	Destabilizing	1.0	D	0.706	prob.neutral	N	0.486991051	None	None	N
T/P	0.8459	likely_pathogenic	0.8575	pathogenic	-0.487	Destabilizing	1.0	D	0.783	deleterious	D	0.523348691	None	None	N
T/Q	0.5754	likely_pathogenic	0.5705	pathogenic	-1.161	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
T/R	0.4524	ambiguous	0.4444	ambiguous	-0.375	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
T/S	0.2749	likely_benign	0.2708	benign	-0.955	Destabilizing	0.999	D	0.476	neutral	N	0.479192482	None	None	N
T/V	0.2181	likely_benign	0.2129	benign	-0.487	Destabilizing	0.999	D	0.56	neutral	None	None	None	None	N
T/W	0.8634	likely_pathogenic	0.8403	pathogenic	-1.179	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
T/Y	0.5672	likely_pathogenic	0.5497	ambiguous	-0.843	Destabilizing	1.0	D	0.788	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.