TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31600	95023;95024;95025	chr2:178546630;178546629;178546628	chr2:179411357;179411356;179411355
N2AB	29959	90100;90101;90102	chr2:178546630;178546629;178546628	chr2:179411357;179411356;179411355
N2A	29032	87319;87320;87321	chr2:178546630;178546629;178546628	chr2:179411357;179411356;179411355
N2B	22535	67828;67829;67830	chr2:178546630;178546629;178546628	chr2:179411357;179411356;179411355
Novex-1	22660	68203;68204;68205	chr2:178546630;178546629;178546628	chr2:179411357;179411356;179411355
Novex-2	22727	68404;68405;68406	chr2:178546630;178546629;178546628	chr2:179411357;179411356;179411355
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: Fn3-118
• Domain position: 95
• Structural Position: 124
• Q(SASA): 0.1143
• 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/A	rs1363231803	-1.307	0.807	N	0.643	0.257	0.227260227426	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
T/A	rs1363231803	-1.307	0.807	N	0.643	0.257	0.227260227426	gnomAD-4.0.0	2.05454E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.70103E-06	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	0.3597	ambiguous	0.3448	ambiguous	-1.135	Destabilizing	0.807	D	0.643	neutral	N	0.486605295	None	None	N
T/C	0.8322	likely_pathogenic	0.8142	pathogenic	-0.83	Destabilizing	1.0	D	0.558	neutral	None	None	None	None	N
T/D	0.9816	likely_pathogenic	0.9742	pathogenic	-1.141	Destabilizing	0.99	D	0.575	neutral	None	None	None	None	N
T/E	0.9831	likely_pathogenic	0.9769	pathogenic	-0.971	Destabilizing	0.99	D	0.564	neutral	None	None	None	None	N
T/F	0.9747	likely_pathogenic	0.9661	pathogenic	-0.789	Destabilizing	0.998	D	0.807	deleterious	None	None	None	None	N
T/G	0.8044	likely_pathogenic	0.7841	pathogenic	-1.548	Destabilizing	0.964	D	0.721	deleterious	None	None	None	None	N
T/H	0.9697	likely_pathogenic	0.9638	pathogenic	-1.667	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
T/I	0.8942	likely_pathogenic	0.8513	pathogenic	-0.061	Destabilizing	0.993	D	0.523	neutral	N	0.467046236	None	None	N
T/K	0.9808	likely_pathogenic	0.9753	pathogenic	-0.679	Destabilizing	0.986	D	0.564	neutral	N	0.487872743	None	None	N
T/L	0.7008	likely_pathogenic	0.6533	pathogenic	-0.061	Destabilizing	0.982	D	0.613	neutral	None	None	None	None	N
T/M	0.5843	likely_pathogenic	0.5252	ambiguous	-0.017	Destabilizing	1.0	D	0.553	neutral	None	None	None	None	N
T/N	0.8913	likely_pathogenic	0.8483	pathogenic	-1.229	Destabilizing	0.99	D	0.607	neutral	None	None	None	None	N
T/P	0.8627	likely_pathogenic	0.8282	pathogenic	-0.386	Destabilizing	0.993	D	0.517	neutral	N	0.467299726	None	None	N
T/Q	0.9617	likely_pathogenic	0.9539	pathogenic	-1.062	Destabilizing	0.995	D	0.479	neutral	None	None	None	None	N
T/R	0.9636	likely_pathogenic	0.9561	pathogenic	-0.801	Destabilizing	0.993	D	0.5	neutral	N	0.510838843	None	None	N
T/S	0.2628	likely_benign	0.2459	benign	-1.503	Destabilizing	0.441	N	0.36	neutral	N	0.397290669	None	None	N
T/V	0.6536	likely_pathogenic	0.5986	pathogenic	-0.386	Destabilizing	0.982	D	0.599	neutral	None	None	None	None	N
T/W	0.9939	likely_pathogenic	0.9919	pathogenic	-0.871	Destabilizing	1.0	D	0.701	prob.delet.	None	None	None	None	N
T/Y	0.9844	likely_pathogenic	0.9781	pathogenic	-0.534	Destabilizing	0.998	D	0.809	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.