TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10118	30577;30578;30579	chr2:178702535;178702534;178702533	chr2:179567262;179567261;179567260
N2AB	9801	29626;29627;29628	chr2:178702535;178702534;178702533	chr2:179567262;179567261;179567260
N2A	8874	26845;26846;26847	chr2:178702535;178702534;178702533	chr2:179567262;179567261;179567260
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-86
• Domain position: 41
• Structural Position: 59
• Q(SASA): 0.6101
• 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/K	None	None	None	None	0.083	0.144	0.0482279557977	gnomAD-4.0.0	1.59085E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85745E-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
T/A	0.16	likely_benign	0.1295	benign	-0.456	Destabilizing	0.022	N	0.144	neutral	None	None	None	None	N
T/C	0.7535	likely_pathogenic	0.6938	pathogenic	-0.506	Destabilizing	0.781	D	0.319	neutral	None	None	None	None	N
T/D	0.7478	likely_pathogenic	0.6792	pathogenic	0.414	Stabilizing	0.142	N	0.385	neutral	None	None	None	None	N
T/E	0.4404	ambiguous	0.3568	ambiguous	0.4	Stabilizing	0.033	N	0.299	neutral	None	None	None	None	N
T/F	0.4955	ambiguous	0.4384	ambiguous	-0.937	Destabilizing	0.076	N	0.459	neutral	None	None	None	None	N
T/G	0.5315	ambiguous	0.4618	ambiguous	-0.614	Destabilizing	0.064	N	0.365	neutral	None	None	None	None	N
T/H	0.4678	ambiguous	0.3548	ambiguous	-0.668	Destabilizing	0.54	D	0.388	neutral	None	None	None	None	N
T/I	0.1748	likely_benign	0.1654	benign	-0.144	Destabilizing	None	N	0.085	neutral	None	None	None	None	N
T/K	0.2393	likely_benign	0.1762	benign	-0.175	Destabilizing	None	N	0.083	neutral	None	None	None	None	N
T/L	0.1538	likely_benign	0.1312	benign	-0.144	Destabilizing	None	N	0.085	neutral	None	None	None	None	N
T/M	0.1239	likely_benign	0.1093	benign	-0.344	Destabilizing	0.367	N	0.349	neutral	None	None	None	None	N
T/N	0.3131	likely_benign	0.2572	benign	-0.255	Destabilizing	0.142	N	0.213	neutral	None	None	None	None	N
T/P	0.413	ambiguous	0.36	ambiguous	-0.219	Destabilizing	0.202	N	0.397	neutral	None	None	None	None	N
T/Q	0.2626	likely_benign	0.2038	benign	-0.299	Destabilizing	0.001	N	0.097	neutral	None	None	None	None	N
T/R	0.2278	likely_benign	0.1489	benign	0.027	Stabilizing	None	N	0.086	neutral	None	None	None	None	N
T/S	0.2642	likely_benign	0.2139	benign	-0.508	Destabilizing	0.049	N	0.186	neutral	None	None	None	None	N
T/V	0.1678	likely_benign	0.1568	benign	-0.219	Destabilizing	0.005	N	0.141	neutral	None	None	None	None	N
T/W	0.8194	likely_pathogenic	0.751	pathogenic	-1.001	Destabilizing	0.931	D	0.368	neutral	None	None	None	None	N
T/Y	0.6195	likely_pathogenic	0.5436	ambiguous	-0.661	Destabilizing	0.54	D	0.449	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.