TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19441	58546;58547;58548	chr2:178594072;178594071;178594070	chr2:179458799;179458798;179458797
N2AB	17800	53623;53624;53625	chr2:178594072;178594071;178594070	chr2:179458799;179458798;179458797
N2A	16873	50842;50843;50844	chr2:178594072;178594071;178594070	chr2:179458799;179458798;179458797
N2B	10376	31351;31352;31353	chr2:178594072;178594071;178594070	chr2:179458799;179458798;179458797
Novex-1	10501	31726;31727;31728	chr2:178594072;178594071;178594070	chr2:179458799;179458798;179458797
Novex-2	10568	31927;31928;31929	chr2:178594072;178594071;178594070	chr2:179458799;179458798;179458797
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-118
• Domain position: 51
• Structural Position: 135
• Q(SASA): 0.3555
• 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	0.98	N	0.475	0.251	0.444505407614	gnomAD-4.0.0	1.59185E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43299E-05	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	0.0884	likely_benign	0.0874	benign	-0.915	Destabilizing	0.98	D	0.475	neutral	N	0.507142379	None	None	N
T/C	0.3635	ambiguous	0.3394	benign	-0.538	Destabilizing	1.0	D	0.652	neutral	None	None	None	None	N
T/D	0.4333	ambiguous	0.4433	ambiguous	-0.409	Destabilizing	0.942	D	0.563	neutral	None	None	None	None	N
T/E	0.3232	likely_benign	0.336	benign	-0.364	Destabilizing	0.97	D	0.573	neutral	None	None	None	None	N
T/F	0.1562	likely_benign	0.1521	benign	-0.843	Destabilizing	0.996	D	0.694	prob.neutral	None	None	None	None	N
T/G	0.2678	likely_benign	0.2617	benign	-1.222	Destabilizing	0.97	D	0.635	neutral	None	None	None	None	N
T/H	0.2235	likely_benign	0.2154	benign	-1.5	Destabilizing	0.092	N	0.436	neutral	None	None	None	None	N
T/I	0.1402	likely_benign	0.1396	benign	-0.173	Destabilizing	0.998	D	0.634	neutral	D	0.523053194	None	None	N
T/K	0.2325	likely_benign	0.2512	benign	-0.722	Destabilizing	0.961	D	0.559	neutral	N	0.509142534	None	None	N
T/L	0.0938	likely_benign	0.0943	benign	-0.173	Destabilizing	0.985	D	0.575	neutral	None	None	None	None	N
T/M	0.0816	likely_benign	0.0792	benign	0.085	Stabilizing	1.0	D	0.639	neutral	None	None	None	None	N
T/N	0.1266	likely_benign	0.1315	benign	-0.796	Destabilizing	0.304	N	0.314	neutral	None	None	None	None	N
T/P	0.6619	likely_pathogenic	0.7461	pathogenic	-0.387	Destabilizing	0.998	D	0.633	neutral	D	0.535387773	None	None	N
T/Q	0.2337	likely_benign	0.2367	benign	-0.886	Destabilizing	0.996	D	0.637	neutral	None	None	None	None	N
T/R	0.1977	likely_benign	0.2103	benign	-0.592	Destabilizing	0.989	D	0.579	neutral	N	0.476280755	None	None	N
T/S	0.0996	likely_benign	0.0984	benign	-1.083	Destabilizing	0.961	D	0.489	neutral	N	0.459311147	None	None	N
T/V	0.1126	likely_benign	0.105	benign	-0.387	Destabilizing	0.995	D	0.492	neutral	None	None	None	None	N
T/W	0.5636	ambiguous	0.5618	ambiguous	-0.804	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
T/Y	0.2014	likely_benign	0.2097	benign	-0.554	Destabilizing	0.991	D	0.696	prob.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.