TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24168	72727;72728;72729	chr2:178573630;178573629;178573628	chr2:179438357;179438356;179438355
N2AB	22527	67804;67805;67806	chr2:178573630;178573629;178573628	chr2:179438357;179438356;179438355
N2A	21600	65023;65024;65025	chr2:178573630;178573629;178573628	chr2:179438357;179438356;179438355
N2B	15103	45532;45533;45534	chr2:178573630;178573629;178573628	chr2:179438357;179438356;179438355
Novex-1	15228	45907;45908;45909	chr2:178573630;178573629;178573628	chr2:179438357;179438356;179438355
Novex-2	15295	46108;46109;46110	chr2:178573630;178573629;178573628	chr2:179438357;179438356;179438355
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Fn3-63
• Domain position: 47
• Structural Position: 63
• Q(SASA): 1.0298
• 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
L/S	None	None	0.988	N	0.534	0.435	0.750485479121	gnomAD-4.0.0	1.9379E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.35891E-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
L/A	0.7975	likely_pathogenic	0.8377	pathogenic	-0.439	Destabilizing	0.938	D	0.528	neutral	None	None	None	None	N
L/C	0.9359	likely_pathogenic	0.9622	pathogenic	-0.788	Destabilizing	1.0	D	0.625	neutral	None	None	None	None	N
L/D	0.9822	likely_pathogenic	0.9873	pathogenic	-0.169	Destabilizing	0.991	D	0.655	neutral	None	None	None	None	N
L/E	0.9173	likely_pathogenic	0.9352	pathogenic	-0.259	Destabilizing	0.995	D	0.647	neutral	None	None	None	None	N
L/F	0.6486	likely_pathogenic	0.7445	pathogenic	-0.584	Destabilizing	0.998	D	0.601	neutral	N	0.511122467	None	None	N
L/G	0.947	likely_pathogenic	0.963	pathogenic	-0.539	Destabilizing	0.086	N	0.477	neutral	None	None	None	None	N
L/H	0.8605	likely_pathogenic	0.9095	pathogenic	0.122	Stabilizing	1.0	D	0.673	neutral	None	None	None	None	N
L/I	0.198	likely_benign	0.2407	benign	-0.295	Destabilizing	0.995	D	0.519	neutral	None	None	None	None	N
L/K	0.8332	likely_pathogenic	0.8526	pathogenic	-0.314	Destabilizing	0.991	D	0.597	neutral	None	None	None	None	N
L/M	0.3138	likely_benign	0.3731	ambiguous	-0.593	Destabilizing	0.998	D	0.613	neutral	N	0.517806798	None	None	N
L/N	0.9165	likely_pathogenic	0.9413	pathogenic	-0.193	Destabilizing	0.991	D	0.651	neutral	None	None	None	None	N
L/P	0.8268	likely_pathogenic	0.8924	pathogenic	-0.315	Destabilizing	0.998	D	0.661	neutral	None	None	None	None	N
L/Q	0.7631	likely_pathogenic	0.833	pathogenic	-0.362	Destabilizing	0.998	D	0.622	neutral	None	None	None	None	N
L/R	0.756	likely_pathogenic	0.7981	pathogenic	0.141	Stabilizing	0.995	D	0.612	neutral	None	None	None	None	N
L/S	0.9114	likely_pathogenic	0.9505	pathogenic	-0.586	Destabilizing	0.988	D	0.534	neutral	N	0.486329098	None	None	N
L/T	0.8035	likely_pathogenic	0.8639	pathogenic	-0.575	Destabilizing	0.995	D	0.578	neutral	None	None	None	None	N
L/V	0.2871	likely_benign	0.3475	ambiguous	-0.315	Destabilizing	0.979	D	0.53	neutral	N	0.480019201	None	None	N
L/W	0.7893	likely_pathogenic	0.8415	pathogenic	-0.604	Destabilizing	0.999	D	0.677	prob.neutral	N	0.511375956	None	None	N
L/Y	0.8667	likely_pathogenic	0.9015	pathogenic	-0.37	Destabilizing	0.998	D	0.618	neutral	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.