TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25756	77491;77492;77493	chr2:178568866;178568865;178568864	chr2:179433593;179433592;179433591
N2AB	24115	72568;72569;72570	chr2:178568866;178568865;178568864	chr2:179433593;179433592;179433591
N2A	23188	69787;69788;69789	chr2:178568866;178568865;178568864	chr2:179433593;179433592;179433591
N2B	16691	50296;50297;50298	chr2:178568866;178568865;178568864	chr2:179433593;179433592;179433591
Novex-1	16816	50671;50672;50673	chr2:178568866;178568865;178568864	chr2:179433593;179433592;179433591
Novex-2	16883	50872;50873;50874	chr2:178568866;178568865;178568864	chr2:179433593;179433592;179433591
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-75
• Domain position: 59
• Structural Position: 91
• Q(SASA): 0.1891
• 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
A/G	None	None	0.834	N	0.604	0.287	0.324986149311	gnomAD-4.0.0	6.84539E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99609E-07	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	0.4964	ambiguous	0.4619	ambiguous	-0.745	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
A/D	0.8573	likely_pathogenic	0.8339	pathogenic	-0.735	Destabilizing	0.996	D	0.697	prob.neutral	None	None	None	None	N
A/E	0.7557	likely_pathogenic	0.7336	pathogenic	-0.66	Destabilizing	0.996	D	0.729	prob.delet.	N	0.516139351	None	None	N
A/F	0.6131	likely_pathogenic	0.5765	pathogenic	-0.525	Destabilizing	0.998	D	0.73	prob.delet.	None	None	None	None	N
A/G	0.2716	likely_benign	0.2406	benign	-0.972	Destabilizing	0.834	D	0.604	neutral	N	0.481652361	None	None	N
A/H	0.7779	likely_pathogenic	0.7461	pathogenic	-1.233	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
A/I	0.5032	ambiguous	0.4889	ambiguous	0.265	Stabilizing	0.477	N	0.535	neutral	None	None	None	None	N
A/K	0.9011	likely_pathogenic	0.8882	pathogenic	-0.754	Destabilizing	0.998	D	0.729	prob.delet.	None	None	None	None	N
A/L	0.4271	ambiguous	0.3976	ambiguous	0.265	Stabilizing	0.899	D	0.665	neutral	None	None	None	None	N
A/M	0.3734	ambiguous	0.3482	ambiguous	0.03	Stabilizing	0.998	D	0.703	prob.neutral	None	None	None	None	N
A/N	0.7068	likely_pathogenic	0.6822	pathogenic	-0.726	Destabilizing	0.966	D	0.714	prob.delet.	None	None	None	None	N
A/P	0.9805	likely_pathogenic	0.9751	pathogenic	0.019	Stabilizing	0.998	D	0.699	prob.neutral	N	0.516139351	None	None	N
A/Q	0.7874	likely_pathogenic	0.7651	pathogenic	-0.682	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	N
A/R	0.8674	likely_pathogenic	0.8587	pathogenic	-0.733	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
A/S	0.2002	likely_benign	0.1875	benign	-1.203	Destabilizing	0.484	N	0.586	neutral	N	0.486171811	None	None	N
A/T	0.1247	likely_benign	0.1262	benign	-1.001	Destabilizing	0.086	N	0.299	neutral	N	0.468188841	None	None	N
A/V	0.2146	likely_benign	0.2106	benign	0.019	Stabilizing	0.716	D	0.603	neutral	N	0.471570289	None	None	N
A/W	0.9357	likely_pathogenic	0.9254	pathogenic	-1.043	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
A/Y	0.7211	likely_pathogenic	0.6834	pathogenic	-0.494	Destabilizing	0.999	D	0.737	prob.delet.	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.