TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7379	22360;22361;22362	chr2:178722764;178722763;178722762	chr2:179587491;179587490;179587489
N2AB	7062	21409;21410;21411	chr2:178722764;178722763;178722762	chr2:179587491;179587490;179587489
N2A	6135	18628;18629;18630	chr2:178722764;178722763;178722762	chr2:179587491;179587490;179587489
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-58
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.2388
• 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/A	None	None	0.704	N	0.379	0.267	0.295974979623	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.0927	likely_benign	0.1348	benign	-1.259	Destabilizing	0.704	D	0.379	neutral	N	0.485385814	None	None	N
T/C	0.4408	ambiguous	0.5594	ambiguous	-0.733	Destabilizing	0.046	N	0.316	neutral	None	None	None	None	N
T/D	0.608	likely_pathogenic	0.8209	pathogenic	-1.615	Destabilizing	0.939	D	0.523	neutral	None	None	None	None	N
T/E	0.399	ambiguous	0.621	pathogenic	-1.384	Destabilizing	0.939	D	0.536	neutral	None	None	None	None	N
T/F	0.2492	likely_benign	0.4181	ambiguous	-0.871	Destabilizing	0.991	D	0.606	neutral	None	None	None	None	N
T/G	0.3675	ambiguous	0.5369	ambiguous	-1.673	Destabilizing	0.939	D	0.545	neutral	None	None	None	None	N
T/H	0.2542	likely_benign	0.402	ambiguous	-1.687	Destabilizing	0.999	D	0.61	neutral	None	None	None	None	N
T/I	0.1784	likely_benign	0.3083	benign	-0.155	Destabilizing	0.134	N	0.383	neutral	N	0.487234041	None	None	N
T/K	0.219	likely_benign	0.4051	ambiguous	-0.327	Destabilizing	0.92	D	0.519	neutral	N	0.487655328	None	None	N
T/L	0.1203	likely_benign	0.1915	benign	-0.155	Destabilizing	0.759	D	0.475	neutral	None	None	None	None	N
T/M	0.103	likely_benign	0.1365	benign	-0.283	Destabilizing	0.991	D	0.576	neutral	None	None	None	None	N
T/N	0.1815	likely_benign	0.2981	benign	-1.078	Destabilizing	0.982	D	0.527	neutral	None	None	None	None	N
T/P	0.7556	likely_pathogenic	0.9018	pathogenic	-0.495	Destabilizing	0.988	D	0.557	neutral	N	0.49863984	None	None	N
T/Q	0.2424	likely_benign	0.3857	ambiguous	-0.791	Destabilizing	0.991	D	0.566	neutral	None	None	None	None	N
T/R	0.1632	likely_benign	0.3153	benign	-0.635	Destabilizing	0.988	D	0.561	neutral	N	0.469955002	None	None	N
T/S	0.1216	likely_benign	0.1749	benign	-1.289	Destabilizing	0.31	N	0.243	neutral	N	0.411829418	None	None	N
T/V	0.1345	likely_benign	0.1987	benign	-0.495	Destabilizing	0.759	D	0.463	neutral	None	None	None	None	N
T/W	0.6106	likely_pathogenic	0.7769	pathogenic	-1.073	Destabilizing	0.999	D	0.637	neutral	None	None	None	None	N
T/Y	0.2814	likely_benign	0.4276	ambiguous	-0.667	Destabilizing	0.997	D	0.63	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.