TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27251	81976;81977;81978	chr2:178564381;178564380;178564379	chr2:179429108;179429107;179429106
N2AB	25610	77053;77054;77055	chr2:178564381;178564380;178564379	chr2:179429108;179429107;179429106
N2A	24683	74272;74273;74274	chr2:178564381;178564380;178564379	chr2:179429108;179429107;179429106
N2B	18186	54781;54782;54783	chr2:178564381;178564380;178564379	chr2:179429108;179429107;179429106
Novex-1	18311	55156;55157;55158	chr2:178564381;178564380;178564379	chr2:179429108;179429107;179429106
Novex-2	18378	55357;55358;55359	chr2:178564381;178564380;178564379	chr2:179429108;179429107;179429106
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-86
• Domain position: 82
• Structural Position: 114
• Q(SASA): 0.5833
• 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
A/T	None	None	0.958	N	0.741	0.394	0.448099371145	gnomAD-4.0.0	1.59162E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85835E-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
A/C	0.7353	likely_pathogenic	0.7069	pathogenic	-0.697	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
A/D	0.9361	likely_pathogenic	0.9263	pathogenic	-0.483	Destabilizing	0.998	D	0.835	deleterious	N	0.503235655	None	None	I
A/E	0.904	likely_pathogenic	0.8894	pathogenic	-0.647	Destabilizing	0.995	D	0.786	deleterious	None	None	None	None	I
A/F	0.7034	likely_pathogenic	0.6498	pathogenic	-0.923	Destabilizing	0.991	D	0.863	deleterious	None	None	None	None	I
A/G	0.4377	ambiguous	0.4158	ambiguous	-0.155	Destabilizing	0.979	D	0.643	neutral	N	0.501968207	None	None	I
A/H	0.9189	likely_pathogenic	0.9071	pathogenic	-0.175	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
A/I	0.56	ambiguous	0.4692	ambiguous	-0.352	Destabilizing	0.938	D	0.71	prob.delet.	None	None	None	None	I
A/K	0.958	likely_pathogenic	0.9525	pathogenic	-0.327	Destabilizing	0.995	D	0.786	deleterious	None	None	None	None	I
A/L	0.4564	ambiguous	0.4059	ambiguous	-0.352	Destabilizing	0.938	D	0.573	neutral	None	None	None	None	I
A/M	0.5702	likely_pathogenic	0.5028	ambiguous	-0.3	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	I
A/N	0.8211	likely_pathogenic	0.7909	pathogenic	-0.093	Destabilizing	0.998	D	0.859	deleterious	None	None	None	None	I
A/P	0.9628	likely_pathogenic	0.9665	pathogenic	-0.259	Destabilizing	0.998	D	0.791	deleterious	D	0.536939404	None	None	I
A/Q	0.8397	likely_pathogenic	0.8319	pathogenic	-0.408	Destabilizing	0.998	D	0.805	deleterious	None	None	None	None	I
A/R	0.8825	likely_pathogenic	0.8792	pathogenic	0.127	Stabilizing	0.995	D	0.805	deleterious	None	None	None	None	I
A/S	0.1978	likely_benign	0.1802	benign	-0.254	Destabilizing	0.979	D	0.636	neutral	N	0.48753771	None	None	I
A/T	0.3535	ambiguous	0.2969	benign	-0.348	Destabilizing	0.958	D	0.741	deleterious	N	0.503996123	None	None	I
A/V	0.2894	likely_benign	0.2341	benign	-0.259	Destabilizing	0.142	N	0.454	neutral	N	0.477845688	None	None	I
A/W	0.9675	likely_pathogenic	0.9612	pathogenic	-1.02	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	I
A/Y	0.893	likely_pathogenic	0.8752	pathogenic	-0.666	Destabilizing	0.995	D	0.864	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.