TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21540	64843;64844;64845	chr2:178585126;178585125;178585124	chr2:179449853;179449852;179449851
N2AB	19899	59920;59921;59922	chr2:178585126;178585125;178585124	chr2:179449853;179449852;179449851
N2A	18972	57139;57140;57141	chr2:178585126;178585125;178585124	chr2:179449853;179449852;179449851
N2B	12475	37648;37649;37650	chr2:178585126;178585125;178585124	chr2:179449853;179449852;179449851
Novex-1	12600	38023;38024;38025	chr2:178585126;178585125;178585124	chr2:179449853;179449852;179449851
Novex-2	12667	38224;38225;38226	chr2:178585126;178585125;178585124	chr2:179449853;179449852;179449851
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: Ig-124
• Domain position: 72
• Structural Position: 157
• Q(SASA): 0.2294
• 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	rs1284135964	0.51	0.012	N	0.446	0.179	0.29132392195	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
T/I	rs1284135964	0.51	0.012	N	0.446	0.179	0.29132392195	gnomAD-4.0.0	1.36907E-06	None	None	None	None	N	None	0	2.23884E-05	None	0	0	None	0	0	8.99816E-07	0	0
T/R	None	None	0.966	N	0.683	0.333	0.441740949975	gnomAD-4.0.0	6.84537E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.1606E-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
T/A	0.0954	likely_benign	0.0922	benign	-0.881	Destabilizing	0.454	N	0.521	neutral	N	0.521765115	None	None	N
T/C	0.286	likely_benign	0.2673	benign	-0.806	Destabilizing	0.998	D	0.666	neutral	None	None	None	None	N
T/D	0.478	ambiguous	0.4539	ambiguous	-1.467	Destabilizing	0.842	D	0.618	neutral	None	None	None	None	N
T/E	0.2801	likely_benign	0.2737	benign	-1.389	Destabilizing	0.842	D	0.611	neutral	None	None	None	None	N
T/F	0.1943	likely_benign	0.1755	benign	-0.848	Destabilizing	0.949	D	0.733	prob.delet.	None	None	None	None	N
T/G	0.3293	likely_benign	0.3075	benign	-1.199	Destabilizing	0.842	D	0.663	neutral	None	None	None	None	N
T/H	0.2038	likely_benign	0.1862	benign	-1.507	Destabilizing	0.998	D	0.726	prob.delet.	None	None	None	None	N
T/I	0.1078	likely_benign	0.0971	benign	-0.098	Destabilizing	0.012	N	0.446	neutral	N	0.472280444	None	None	N
T/K	0.2195	likely_benign	0.2043	benign	-0.823	Destabilizing	0.801	D	0.615	neutral	N	0.475240605	None	None	N
T/L	0.0965	likely_benign	0.0887	benign	-0.098	Destabilizing	0.525	D	0.602	neutral	None	None	None	None	N
T/M	0.0782	likely_benign	0.0802	benign	0.183	Stabilizing	0.949	D	0.683	prob.neutral	None	None	None	None	N
T/N	0.1701	likely_benign	0.1569	benign	-1.189	Destabilizing	0.842	D	0.606	neutral	None	None	None	None	N
T/P	0.792	likely_pathogenic	0.7543	pathogenic	-0.326	Destabilizing	0.966	D	0.672	neutral	N	0.502065972	None	None	N
T/Q	0.1946	likely_benign	0.1928	benign	-1.288	Destabilizing	0.974	D	0.692	prob.neutral	None	None	None	None	N
T/R	0.186	likely_benign	0.1707	benign	-0.685	Destabilizing	0.966	D	0.683	prob.neutral	N	0.449152868	None	None	N
T/S	0.1173	likely_benign	0.1128	benign	-1.324	Destabilizing	0.062	N	0.287	neutral	N	0.45496412	None	None	N
T/V	0.0929	likely_benign	0.0866	benign	-0.326	Destabilizing	0.525	D	0.591	neutral	None	None	None	None	N
T/W	0.5071	ambiguous	0.4875	ambiguous	-0.907	Destabilizing	0.998	D	0.751	deleterious	None	None	None	None	N
T/Y	0.2394	likely_benign	0.2175	benign	-0.579	Destabilizing	0.991	D	0.743	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.