TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31111	93556;93557;93558	chr2:178548295;178548294;178548293	chr2:179413022;179413021;179413020
N2AB	29470	88633;88634;88635	chr2:178548295;178548294;178548293	chr2:179413022;179413021;179413020
N2A	28543	85852;85853;85854	chr2:178548295;178548294;178548293	chr2:179413022;179413021;179413020
N2B	22046	66361;66362;66363	chr2:178548295;178548294;178548293	chr2:179413022;179413021;179413020
Novex-1	22171	66736;66737;66738	chr2:178548295;178548294;178548293	chr2:179413022;179413021;179413020
Novex-2	22238	66937;66938;66939	chr2:178548295;178548294;178548293	chr2:179413022;179413021;179413020
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: Fn3-114
• Domain position: 96
• Structural Position: 131
• Q(SASA): 0.2949
• 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	0.997	N	0.48	0.329	0.171388866994	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	0.1265	likely_benign	0.119	benign	-0.388	Destabilizing	0.997	D	0.48	neutral	N	0.399803405	None	None	N
T/C	0.6114	likely_pathogenic	0.6329	pathogenic	-0.395	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
T/D	0.8913	likely_pathogenic	0.8566	pathogenic	0.227	Stabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N
T/E	0.7664	likely_pathogenic	0.7126	pathogenic	0.152	Stabilizing	0.999	D	0.689	prob.delet.	None	None	None	None	N
T/F	0.7937	likely_pathogenic	0.7554	pathogenic	-0.87	Destabilizing	0.999	D	0.643	neutral	None	None	None	None	N
T/G	0.4056	ambiguous	0.3822	ambiguous	-0.511	Destabilizing	0.999	D	0.571	neutral	None	None	None	None	N
T/H	0.7461	likely_pathogenic	0.691	pathogenic	-0.818	Destabilizing	1.0	D	0.657	prob.neutral	None	None	None	None	N
T/I	0.64	likely_pathogenic	0.619	pathogenic	-0.183	Destabilizing	0.999	D	0.665	prob.neutral	N	0.459851786	None	None	N
T/K	0.5136	ambiguous	0.3999	ambiguous	-0.413	Destabilizing	0.999	D	0.69	prob.delet.	N	0.40434522	None	None	N
T/L	0.2969	likely_benign	0.2788	benign	-0.183	Destabilizing	0.998	D	0.676	prob.neutral	None	None	None	None	N
T/M	0.1628	likely_benign	0.1611	benign	-0.073	Destabilizing	1.0	D	0.657	prob.neutral	None	None	None	None	N
T/N	0.4968	ambiguous	0.4286	ambiguous	-0.237	Destabilizing	0.999	D	0.705	prob.delet.	None	None	None	None	N
T/P	0.7908	likely_pathogenic	0.7231	pathogenic	-0.223	Destabilizing	0.999	D	0.623	neutral	N	0.434259908	None	None	N
T/Q	0.5093	ambiguous	0.4569	ambiguous	-0.452	Destabilizing	0.999	D	0.673	prob.neutral	None	None	None	None	N
T/R	0.4126	ambiguous	0.3211	benign	-0.17	Destabilizing	0.999	D	0.635	neutral	N	0.431723822	None	None	N
T/S	0.194	likely_benign	0.18	benign	-0.451	Destabilizing	0.997	D	0.547	neutral	N	0.390279844	None	None	N
T/V	0.3362	likely_benign	0.3373	benign	-0.223	Destabilizing	0.998	D	0.629	neutral	None	None	None	None	N
T/W	0.9434	likely_pathogenic	0.9334	pathogenic	-0.867	Destabilizing	1.0	D	0.595	neutral	None	None	None	None	N
T/Y	0.8575	likely_pathogenic	0.8116	pathogenic	-0.589	Destabilizing	1.0	D	0.654	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.