TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14131	42616;42617;42618	chr2:178634390;178634389;178634388	chr2:179499117;179499116;179499115
N2AB	12490	37693;37694;37695	chr2:178634390;178634389;178634388	chr2:179499117;179499116;179499115
N2A	11563	34912;34913;34914	chr2:178634390;178634389;178634388	chr2:179499117;179499116;179499115
N2B	5066	15421;15422;15423	chr2:178634390;178634389;178634388	chr2:179499117;179499116;179499115
Novex-1	5191	15796;15797;15798	chr2:178634390;178634389;178634388	chr2:179499117;179499116;179499115
Novex-2	5258	15997;15998;15999	chr2:178634390;178634389;178634388	chr2:179499117;179499116;179499115
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-91
• Domain position: 78
• Structural Position: 170
• Q(SASA): 0.1309
• 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/N	None	None	0.062	D	0.63	0.224	0.18995819373	gnomAD-4.0.0	6.86343E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00343E-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
T/A	0.1234	likely_benign	0.2847	benign	-1.054	Destabilizing	0.001	N	0.289	neutral	N	0.44375616	None	None	N
T/C	0.5116	ambiguous	0.7513	pathogenic	-0.535	Destabilizing	0.555	D	0.627	neutral	None	None	None	None	N
T/D	0.7672	likely_pathogenic	0.8969	pathogenic	-0.345	Destabilizing	0.081	N	0.621	neutral	None	None	None	None	N
T/E	0.7546	likely_pathogenic	0.908	pathogenic	-0.255	Destabilizing	0.081	N	0.627	neutral	None	None	None	None	N
T/F	0.6887	likely_pathogenic	0.8948	pathogenic	-0.81	Destabilizing	0.555	D	0.637	neutral	None	None	None	None	N
T/G	0.4074	ambiguous	0.595	pathogenic	-1.41	Destabilizing	0.035	N	0.589	neutral	None	None	None	None	N
T/H	0.6742	likely_pathogenic	0.8448	pathogenic	-1.486	Destabilizing	0.555	D	0.612	neutral	None	None	None	None	N
T/I	0.5471	ambiguous	0.8326	pathogenic	-0.163	Destabilizing	0.117	N	0.617	neutral	D	0.58645716	None	None	N
T/K	0.8037	likely_pathogenic	0.9409	pathogenic	-0.646	Destabilizing	0.081	N	0.627	neutral	None	None	None	None	N
T/L	0.3494	ambiguous	0.6269	pathogenic	-0.163	Destabilizing	0.067	N	0.607	neutral	None	None	None	None	N
T/M	0.2303	likely_benign	0.4363	ambiguous	0.029	Stabilizing	0.791	D	0.634	neutral	None	None	None	None	N
T/N	0.3181	likely_benign	0.4824	ambiguous	-0.833	Destabilizing	0.062	N	0.63	neutral	D	0.587793178	None	None	N
T/P	0.8512	likely_pathogenic	0.9293	pathogenic	-0.427	Destabilizing	0.117	N	0.617	neutral	D	0.58929604	None	None	N
T/Q	0.6614	likely_pathogenic	0.8662	pathogenic	-0.816	Destabilizing	0.38	N	0.661	neutral	None	None	None	None	N
T/R	0.7465	likely_pathogenic	0.9232	pathogenic	-0.572	Destabilizing	0.149	N	0.64	neutral	None	None	None	None	N
T/S	0.1178	likely_benign	0.1425	benign	-1.194	Destabilizing	None	N	0.273	neutral	N	0.412354981	None	None	N
T/V	0.3732	ambiguous	0.6647	pathogenic	-0.427	Destabilizing	0.067	N	0.609	neutral	None	None	None	None	N
T/W	0.9327	likely_pathogenic	0.9827	pathogenic	-0.772	Destabilizing	0.935	D	0.63	neutral	None	None	None	None	N
T/Y	0.6359	likely_pathogenic	0.864	pathogenic	-0.519	Destabilizing	0.555	D	0.633	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.