TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27220	81883;81884;81885	chr2:178564474;178564473;178564472	chr2:179429201;179429200;179429199
N2AB	25579	76960;76961;76962	chr2:178564474;178564473;178564472	chr2:179429201;179429200;179429199
N2A	24652	74179;74180;74181	chr2:178564474;178564473;178564472	chr2:179429201;179429200;179429199
N2B	18155	54688;54689;54690	chr2:178564474;178564473;178564472	chr2:179429201;179429200;179429199
Novex-1	18280	55063;55064;55065	chr2:178564474;178564473;178564472	chr2:179429201;179429200;179429199
Novex-2	18347	55264;55265;55266	chr2:178564474;178564473;178564472	chr2:179429201;179429200;179429199
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-86
• Domain position: 51
• Structural Position: 68
• Q(SASA): 0.2163
• Predicted PPI site: I

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
A/V	rs1356967920	None	1.0	N	0.63	0.435	0.506373324096	gnomAD-4.0.0	6.85005E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	1.65865E-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
A/C	0.5966	likely_pathogenic	0.6108	pathogenic	-0.182	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	I
A/D	0.9772	likely_pathogenic	0.9633	pathogenic	-0.404	Destabilizing	1.0	D	0.705	prob.neutral	N	0.501652266	None	None	I
A/E	0.9634	likely_pathogenic	0.9442	pathogenic	-0.276	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
A/F	0.9192	likely_pathogenic	0.8815	pathogenic	-0.206	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
A/G	0.427	ambiguous	0.3779	ambiguous	-0.696	Destabilizing	1.0	D	0.585	neutral	N	0.493449512	None	None	I
A/H	0.978	likely_pathogenic	0.9709	pathogenic	-1.081	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
A/I	0.7533	likely_pathogenic	0.6868	pathogenic	0.73	Stabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
A/K	0.9927	likely_pathogenic	0.9889	pathogenic	-0.325	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	I
A/L	0.7352	likely_pathogenic	0.6914	pathogenic	0.73	Stabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
A/M	0.7408	likely_pathogenic	0.6897	pathogenic	0.517	Stabilizing	1.0	D	0.758	deleterious	None	None	None	None	I
A/N	0.9215	likely_pathogenic	0.8966	pathogenic	-0.394	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
A/P	0.9849	likely_pathogenic	0.9803	pathogenic	0.437	Stabilizing	1.0	D	0.737	prob.delet.	N	0.506767601	None	None	I
A/Q	0.956	likely_pathogenic	0.9445	pathogenic	-0.232	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	I
A/R	0.9851	likely_pathogenic	0.9788	pathogenic	-0.527	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
A/S	0.2506	likely_benign	0.2244	benign	-0.878	Destabilizing	1.0	D	0.578	neutral	N	0.484357705	None	None	I
A/T	0.3263	likely_benign	0.295	benign	-0.609	Destabilizing	1.0	D	0.683	prob.neutral	N	0.482534053	None	None	I
A/V	0.3541	ambiguous	0.3066	benign	0.437	Stabilizing	1.0	D	0.63	neutral	N	0.475901461	None	None	I
A/W	0.9936	likely_pathogenic	0.9905	pathogenic	-0.851	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
A/Y	0.959	likely_pathogenic	0.943	pathogenic	-0.201	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I

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.