TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9138	27637;27638;27639	chr2:178712510;178712509;178712508	chr2:179577237;179577236;179577235
N2AB	8821	26686;26687;26688	chr2:178712510;178712509;178712508	chr2:179577237;179577236;179577235
N2A	7894	23905;23906;23907	chr2:178712510;178712509;178712508	chr2:179577237;179577236;179577235
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: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-77
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.3615
• 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	0.126	N	0.389	0.214	0.346315397577	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	0	0
T/N	None	None	0.89	N	0.551	0.163	0.39162414616	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	0.1377	likely_benign	0.1432	benign	-0.207	Destabilizing	0.489	N	0.537	neutral	D	0.524669347	None	None	N
T/C	0.6728	likely_pathogenic	0.6451	pathogenic	-0.273	Destabilizing	0.994	D	0.605	neutral	None	None	None	None	N
T/D	0.321	likely_benign	0.4087	ambiguous	0.051	Stabilizing	0.956	D	0.518	neutral	None	None	None	None	N
T/E	0.3301	likely_benign	0.4182	ambiguous	-0.03	Destabilizing	0.915	D	0.517	neutral	None	None	None	None	N
T/F	0.2486	likely_benign	0.3014	benign	-0.745	Destabilizing	0.978	D	0.673	neutral	None	None	None	None	N
T/G	0.439	ambiguous	0.4318	ambiguous	-0.314	Destabilizing	0.754	D	0.615	neutral	None	None	None	None	N
T/H	0.3026	likely_benign	0.3661	ambiguous	-0.519	Destabilizing	0.994	D	0.693	prob.neutral	None	None	None	None	N
T/I	0.2094	likely_benign	0.2909	benign	-0.046	Destabilizing	0.126	N	0.389	neutral	N	0.514743142	None	None	N
T/K	0.2978	likely_benign	0.4292	ambiguous	-0.346	Destabilizing	0.915	D	0.52	neutral	None	None	None	None	N
T/L	0.1453	likely_benign	0.1669	benign	-0.046	Destabilizing	0.754	D	0.533	neutral	None	None	None	None	N
T/M	0.1094	likely_benign	0.1186	benign	-0.048	Destabilizing	0.994	D	0.591	neutral	None	None	None	None	N
T/N	0.1132	likely_benign	0.1431	benign	-0.085	Destabilizing	0.89	D	0.551	neutral	N	0.503389998	None	None	N
T/P	0.4453	ambiguous	0.3644	ambiguous	-0.072	Destabilizing	0.971	D	0.569	neutral	N	0.51735907	None	None	N
T/Q	0.2812	likely_benign	0.3443	ambiguous	-0.304	Destabilizing	0.956	D	0.579	neutral	None	None	None	None	N
T/R	0.2771	likely_benign	0.3783	ambiguous	-0.044	Destabilizing	0.956	D	0.565	neutral	None	None	None	None	N
T/S	0.1012	likely_benign	0.096	benign	-0.26	Destabilizing	0.014	N	0.393	neutral	N	0.476280755	None	None	N
T/V	0.1864	likely_benign	0.2466	benign	-0.072	Destabilizing	0.754	D	0.522	neutral	None	None	None	None	N
T/W	0.6618	likely_pathogenic	0.6881	pathogenic	-0.805	Destabilizing	0.998	D	0.729	prob.delet.	None	None	None	None	N
T/Y	0.2913	likely_benign	0.3424	ambiguous	-0.5	Destabilizing	0.993	D	0.68	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.