TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30739	92440;92441;92442	chr2:178549411;178549410;178549409	chr2:179414138;179414137;179414136
N2AB	29098	87517;87518;87519	chr2:178549411;178549410;178549409	chr2:179414138;179414137;179414136
N2A	28171	84736;84737;84738	chr2:178549411;178549410;178549409	chr2:179414138;179414137;179414136
N2B	21674	65245;65246;65247	chr2:178549411;178549410;178549409	chr2:179414138;179414137;179414136
Novex-1	21799	65620;65621;65622	chr2:178549411;178549410;178549409	chr2:179414138;179414137;179414136
Novex-2	21866	65821;65822;65823	chr2:178549411;178549410;178549409	chr2:179414138;179414137;179414136
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: Fn3-112
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.34
• 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	0.988	N	0.523	0.372	0.537402380065	gnomAD-4.0.0	1.59172E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02535E-05

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	0.0937	likely_benign	0.1143	benign	-1.035	Destabilizing	0.826	D	0.427	neutral	N	0.471709149	None	None	N
T/C	0.2551	likely_benign	0.3131	benign	-0.645	Destabilizing	0.046	N	0.323	neutral	None	None	None	None	N
T/D	0.5323	ambiguous	0.6268	pathogenic	-0.956	Destabilizing	0.884	D	0.439	neutral	None	None	None	None	N
T/E	0.4239	ambiguous	0.5031	ambiguous	-0.837	Destabilizing	0.939	D	0.501	neutral	None	None	None	None	N
T/F	0.2119	likely_benign	0.2835	benign	-0.699	Destabilizing	0.997	D	0.593	neutral	None	None	None	None	N
T/G	0.2376	likely_benign	0.3044	benign	-1.411	Destabilizing	0.939	D	0.461	neutral	None	None	None	None	N
T/H	0.2185	likely_benign	0.269	benign	-1.592	Destabilizing	0.998	D	0.597	neutral	None	None	None	None	N
T/I	0.1549	likely_benign	0.1731	benign	-0.078	Destabilizing	0.988	D	0.523	neutral	N	0.492261424	None	None	N
T/K	0.2934	likely_benign	0.3454	ambiguous	-0.748	Destabilizing	0.92	D	0.477	neutral	N	0.51419049	None	None	N
T/L	0.0924	likely_benign	0.1087	benign	-0.078	Destabilizing	0.939	D	0.419	neutral	None	None	None	None	N
T/M	0.0868	likely_benign	0.0995	benign	0.065	Stabilizing	0.999	D	0.563	neutral	None	None	None	None	N
T/N	0.1246	likely_benign	0.1522	benign	-1.065	Destabilizing	0.17	N	0.392	neutral	None	None	None	None	N
T/P	0.6475	likely_pathogenic	0.7079	pathogenic	-0.364	Destabilizing	0.996	D	0.546	neutral	N	0.51875947	None	None	N
T/Q	0.2322	likely_benign	0.2638	benign	-1.011	Destabilizing	0.991	D	0.541	neutral	None	None	None	None	N
T/R	0.2367	likely_benign	0.2877	benign	-0.753	Destabilizing	0.988	D	0.539	neutral	N	0.508283238	None	None	N
T/S	0.0992	likely_benign	0.119	benign	-1.321	Destabilizing	0.826	D	0.431	neutral	N	0.414964858	None	None	N
T/V	0.1261	likely_benign	0.1472	benign	-0.364	Destabilizing	0.939	D	0.361	neutral	None	None	None	None	N
T/W	0.5468	ambiguous	0.6626	pathogenic	-0.751	Destabilizing	0.999	D	0.621	neutral	None	None	None	None	N
T/Y	0.245	likely_benign	0.3099	benign	-0.46	Destabilizing	0.997	D	0.591	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.