TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23445	70558;70559;70560	chr2:178575799;178575798;178575797	chr2:179440526;179440525;179440524
N2AB	21804	65635;65636;65637	chr2:178575799;178575798;178575797	chr2:179440526;179440525;179440524
N2A	20877	62854;62855;62856	chr2:178575799;178575798;178575797	chr2:179440526;179440525;179440524
N2B	14380	43363;43364;43365	chr2:178575799;178575798;178575797	chr2:179440526;179440525;179440524
Novex-1	14505	43738;43739;43740	chr2:178575799;178575798;178575797	chr2:179440526;179440525;179440524
Novex-2	14572	43939;43940;43941	chr2:178575799;178575798;178575797	chr2:179440526;179440525;179440524
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: Fn3-58
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.3482
• 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	rs1216746795	None	0.625	N	0.335	0.17	0.162503812791	gnomAD-4.0.0	6.00161E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.56251E-06	0	0
T/I	rs750009240	0.065	0.966	D	0.437	0.265	0.383921772103	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	1.15935E-04	None	0	0	None	0	None	0	0	0
T/I	rs750009240	0.065	0.966	D	0.437	0.265	0.383921772103	gnomAD-4.0.0	6.37119E-06	None	None	None	None	N	None	0	9.14913E-05	None	0	0	None	0	0	0	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	0.0719	likely_benign	0.0754	benign	-0.79	Destabilizing	0.625	D	0.335	neutral	N	0.511536974	None	None	N
T/C	0.3169	likely_benign	0.3173	benign	-0.374	Destabilizing	0.998	D	0.415	neutral	None	None	None	None	N
T/D	0.4479	ambiguous	0.4691	ambiguous	-0.564	Destabilizing	0.915	D	0.417	neutral	None	None	None	None	N
T/E	0.3038	likely_benign	0.3339	benign	-0.535	Destabilizing	0.842	D	0.416	neutral	None	None	None	None	N
T/F	0.2599	likely_benign	0.2701	benign	-0.728	Destabilizing	0.991	D	0.507	neutral	None	None	None	None	N
T/G	0.1727	likely_benign	0.1731	benign	-1.091	Destabilizing	0.915	D	0.44	neutral	None	None	None	None	N
T/H	0.2116	likely_benign	0.2156	benign	-1.404	Destabilizing	0.974	D	0.485	neutral	None	None	None	None	N
T/I	0.1459	likely_benign	0.1508	benign	-0.068	Destabilizing	0.966	D	0.437	neutral	D	0.523850123	None	None	N
T/K	0.1433	likely_benign	0.1626	benign	-0.921	Destabilizing	0.454	N	0.416	neutral	N	0.425110068	None	None	N
T/L	0.1001	likely_benign	0.1017	benign	-0.068	Destabilizing	0.688	D	0.417	neutral	None	None	None	None	N
T/M	0.0906	likely_benign	0.0907	benign	0.229	Stabilizing	0.991	D	0.43	neutral	None	None	None	None	N
T/N	0.1436	likely_benign	0.1508	benign	-0.924	Destabilizing	0.842	D	0.335	neutral	None	None	None	None	N
T/P	0.5847	likely_pathogenic	0.577	pathogenic	-0.275	Destabilizing	0.989	D	0.439	neutral	N	0.494592056	None	None	N
T/Q	0.1617	likely_benign	0.1696	benign	-0.984	Destabilizing	0.842	D	0.417	neutral	None	None	None	None	N
T/R	0.1133	likely_benign	0.135	benign	-0.745	Destabilizing	0.002	N	0.172	neutral	N	0.494220649	None	None	N
T/S	0.0977	likely_benign	0.0959	benign	-1.117	Destabilizing	0.625	D	0.387	neutral	N	0.451947165	None	None	N
T/V	0.1001	likely_benign	0.101	benign	-0.275	Destabilizing	0.915	D	0.333	neutral	None	None	None	None	N
T/W	0.5754	likely_pathogenic	0.566	pathogenic	-0.758	Destabilizing	0.998	D	0.521	neutral	None	None	None	None	N
T/Y	0.2973	likely_benign	0.3015	benign	-0.526	Destabilizing	0.991	D	0.509	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.