TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29586	88981;88982;88983	chr2:178554591;178554590;178554589	chr2:179419318;179419317;179419316
N2AB	27945	84058;84059;84060	chr2:178554591;178554590;178554589	chr2:179419318;179419317;179419316
N2A	27018	81277;81278;81279	chr2:178554591;178554590;178554589	chr2:179419318;179419317;179419316
N2B	20521	61786;61787;61788	chr2:178554591;178554590;178554589	chr2:179419318;179419317;179419316
Novex-1	20646	62161;62162;62163	chr2:178554591;178554590;178554589	chr2:179419318;179419317;179419316
Novex-2	20713	62362;62363;62364	chr2:178554591;178554590;178554589	chr2:179419318;179419317;179419316
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-103
• Domain position: 54
• Structural Position: 70
• Q(SASA): 0.2906
• 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
E/K	None	None	0.999	N	0.559	0.339	0.336155897331	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
E/A	0.2128	likely_benign	0.1951	benign	-0.476	Destabilizing	0.999	D	0.658	neutral	N	0.512648908	None	None	N
E/C	0.905	likely_pathogenic	0.8775	pathogenic	-0.163	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
E/D	0.1177	likely_benign	0.1166	benign	-0.373	Destabilizing	0.999	D	0.4	neutral	N	0.489889478	None	None	N
E/F	0.9057	likely_pathogenic	0.8825	pathogenic	-0.221	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
E/G	0.1986	likely_benign	0.1743	benign	-0.7	Destabilizing	1.0	D	0.705	prob.neutral	N	0.505936366	None	None	N
E/H	0.582	likely_pathogenic	0.5441	ambiguous	0.038	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
E/I	0.6423	likely_pathogenic	0.5989	pathogenic	0.094	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/K	0.2383	likely_benign	0.1985	benign	0.171	Stabilizing	0.999	D	0.559	neutral	N	0.516364003	None	None	N
E/L	0.6063	likely_pathogenic	0.5681	pathogenic	0.094	Stabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
E/M	0.6775	likely_pathogenic	0.6389	pathogenic	0.174	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
E/N	0.2833	likely_benign	0.2686	benign	-0.181	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
E/P	0.5119	ambiguous	0.5198	ambiguous	-0.075	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
E/Q	0.1766	likely_benign	0.1635	benign	-0.117	Destabilizing	1.0	D	0.632	neutral	N	0.46668475	None	None	N
E/R	0.3865	ambiguous	0.3366	benign	0.465	Stabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
E/S	0.2014	likely_benign	0.1919	benign	-0.373	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	N
E/T	0.2967	likely_benign	0.2661	benign	-0.184	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
E/V	0.4106	ambiguous	0.3767	ambiguous	-0.075	Destabilizing	1.0	D	0.747	deleterious	N	0.477500261	None	None	N
E/W	0.9599	likely_pathogenic	0.9477	pathogenic	-0.023	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
E/Y	0.7885	likely_pathogenic	0.7571	pathogenic	0.033	Stabilizing	1.0	D	0.741	deleterious	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.