TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20281	61066;61067;61068	chr2:178590884;178590883;178590882	chr2:179455611;179455610;179455609
N2AB	18640	56143;56144;56145	chr2:178590884;178590883;178590882	chr2:179455611;179455610;179455609
N2A	17713	53362;53363;53364	chr2:178590884;178590883;178590882	chr2:179455611;179455610;179455609
N2B	11216	33871;33872;33873	chr2:178590884;178590883;178590882	chr2:179455611;179455610;179455609
Novex-1	11341	34246;34247;34248	chr2:178590884;178590883;178590882	chr2:179455611;179455610;179455609
Novex-2	11408	34447;34448;34449	chr2:178590884;178590883;178590882	chr2:179455611;179455610;179455609
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-35
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.4753
• 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/I	None	None	0.473	N	0.356	0.167	0.319686207203	gnomAD-4.0.0	1.37074E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80213E-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	0.0882	likely_benign	0.0881	benign	-0.338	Destabilizing	0.27	N	0.293	neutral	N	0.511267615	None	None	N
T/C	0.3211	likely_benign	0.2865	benign	-0.241	Destabilizing	0.995	D	0.362	neutral	None	None	None	None	N
T/D	0.3566	ambiguous	0.3408	ambiguous	0.11	Stabilizing	0.704	D	0.382	neutral	None	None	None	None	N
T/E	0.2824	likely_benign	0.2648	benign	0.034	Stabilizing	0.704	D	0.357	neutral	None	None	None	None	N
T/F	0.2221	likely_benign	0.2063	benign	-0.826	Destabilizing	0.007	N	0.296	neutral	None	None	None	None	N
T/G	0.2022	likely_benign	0.206	benign	-0.472	Destabilizing	0.704	D	0.393	neutral	None	None	None	None	N
T/H	0.2188	likely_benign	0.2034	benign	-0.783	Destabilizing	0.017	N	0.288	neutral	None	None	None	None	N
T/I	0.1651	likely_benign	0.1629	benign	-0.105	Destabilizing	0.473	N	0.356	neutral	N	0.494759367	None	None	N
T/K	0.2105	likely_benign	0.2018	benign	-0.37	Destabilizing	0.704	D	0.357	neutral	None	None	None	None	N
T/L	0.0984	likely_benign	0.0993	benign	-0.105	Destabilizing	0.007	N	0.211	neutral	None	None	None	None	N
T/M	0.082	likely_benign	0.0846	benign	0.081	Stabilizing	0.893	D	0.385	neutral	None	None	None	None	N
T/N	0.1194	likely_benign	0.1167	benign	-0.161	Destabilizing	0.642	D	0.231	neutral	N	0.477537757	None	None	N
T/P	0.4542	ambiguous	0.4963	ambiguous	-0.154	Destabilizing	0.927	D	0.463	neutral	N	0.476487801	None	None	N
T/Q	0.2151	likely_benign	0.209	benign	-0.395	Destabilizing	0.893	D	0.46	neutral	None	None	None	None	N
T/R	0.1781	likely_benign	0.1739	benign	-0.093	Destabilizing	0.704	D	0.459	neutral	None	None	None	None	N
T/S	0.1008	likely_benign	0.0965	benign	-0.362	Destabilizing	0.029	N	0.09	neutral	N	0.419624103	None	None	N
T/V	0.1336	likely_benign	0.1277	benign	-0.154	Destabilizing	0.329	N	0.27	neutral	None	None	None	None	N
T/W	0.4903	ambiguous	0.4487	ambiguous	-0.836	Destabilizing	0.985	D	0.348	neutral	None	None	None	None	N
T/Y	0.2345	likely_benign	0.2156	benign	-0.549	Destabilizing	0.003	N	0.223	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.