TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21970	66133;66134;66135	chr2:178582548;178582547;178582546	chr2:179447275;179447274;179447273
N2AB	20329	61210;61211;61212	chr2:178582548;178582547;178582546	chr2:179447275;179447274;179447273
N2A	19402	58429;58430;58431	chr2:178582548;178582547;178582546	chr2:179447275;179447274;179447273
N2B	12905	38938;38939;38940	chr2:178582548;178582547;178582546	chr2:179447275;179447274;179447273
Novex-1	13030	39313;39314;39315	chr2:178582548;178582547;178582546	chr2:179447275;179447274;179447273
Novex-2	13097	39514;39515;39516	chr2:178582548;178582547;178582546	chr2:179447275;179447274;179447273
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-47
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.2444
• 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
S/L	None	None	0.062	N	0.421	0.252	None	gnomAD-4.0.0	2.05488E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.70054E-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
S/A	0.0487	likely_benign	0.0466	benign	-0.373	Destabilizing	None	N	0.067	neutral	N	0.442061033	None	None	N
S/C	0.0995	likely_benign	0.091	benign	-0.696	Destabilizing	0.824	D	0.413	neutral	None	None	None	None	N
S/D	0.6975	likely_pathogenic	0.6819	pathogenic	-1.863	Destabilizing	0.149	N	0.313	neutral	None	None	None	None	N
S/E	0.6372	likely_pathogenic	0.6201	pathogenic	-1.81	Destabilizing	0.149	N	0.332	neutral	None	None	None	None	N
S/F	0.3737	ambiguous	0.3706	ambiguous	-0.564	Destabilizing	0.555	D	0.489	neutral	None	None	None	None	N
S/G	0.0902	likely_benign	0.0832	benign	-0.635	Destabilizing	0.035	N	0.373	neutral	None	None	None	None	N
S/H	0.4754	ambiguous	0.4651	ambiguous	-1.217	Destabilizing	0.935	D	0.412	neutral	None	None	None	None	N
S/I	0.2973	likely_benign	0.3108	benign	0.224	Stabilizing	0.38	N	0.431	neutral	None	None	None	None	N
S/K	0.6738	likely_pathogenic	0.6488	pathogenic	-0.804	Destabilizing	0.149	N	0.34	neutral	None	None	None	None	N
S/L	0.1643	likely_benign	0.1624	benign	0.224	Stabilizing	0.062	N	0.421	neutral	N	0.487719202	None	None	N
S/M	0.2781	likely_benign	0.2727	benign	0.383	Stabilizing	0.555	D	0.417	neutral	None	None	None	None	N
S/N	0.2761	likely_benign	0.2801	benign	-1.219	Destabilizing	0.149	N	0.412	neutral	None	None	None	None	N
S/P	0.1975	likely_benign	0.2626	benign	0.059	Stabilizing	None	N	0.186	neutral	N	0.510459538	None	None	N
S/Q	0.4906	ambiguous	0.478	ambiguous	-1.339	Destabilizing	0.555	D	0.373	neutral	None	None	None	None	N
S/R	0.5972	likely_pathogenic	0.5684	pathogenic	-0.715	Destabilizing	0.38	N	0.385	neutral	None	None	None	None	N
S/T	0.1353	likely_benign	0.1315	benign	-0.886	Destabilizing	0.002	N	0.099	neutral	N	0.473663417	None	None	N
S/V	0.2262	likely_benign	0.2395	benign	0.059	Stabilizing	0.081	N	0.421	neutral	None	None	None	None	N
S/W	0.5498	ambiguous	0.5243	ambiguous	-0.783	Destabilizing	0.935	D	0.578	neutral	None	None	None	None	N
S/Y	0.3558	ambiguous	0.3292	benign	-0.376	Destabilizing	0.555	D	0.493	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.