TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30988	93187;93188;93189	chr2:178548664;178548663;178548662	chr2:179413391;179413390;179413389
N2AB	29347	88264;88265;88266	chr2:178548664;178548663;178548662	chr2:179413391;179413390;179413389
N2A	28420	85483;85484;85485	chr2:178548664;178548663;178548662	chr2:179413391;179413390;179413389
N2B	21923	65992;65993;65994	chr2:178548664;178548663;178548662	chr2:179413391;179413390;179413389
Novex-1	22048	66367;66368;66369	chr2:178548664;178548663;178548662	chr2:179413391;179413390;179413389
Novex-2	22115	66568;66569;66570	chr2:178548664;178548663;178548662	chr2:179413391;179413390;179413389
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-150
• Domain position: 62
• Structural Position: 146
• Q(SASA): 0.8177
• 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
R/K	None	None	0.997	N	0.595	0.293	0.185906805712	gnomAD-4.0.0	1.59116E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02444E-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
R/A	0.9469	likely_pathogenic	0.9467	pathogenic	-0.007	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	I
R/C	0.6277	likely_pathogenic	0.6336	pathogenic	-0.111	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
R/D	0.9904	likely_pathogenic	0.989	pathogenic	-0.182	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
R/E	0.9262	likely_pathogenic	0.9132	pathogenic	-0.13	Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	I
R/F	0.9629	likely_pathogenic	0.9645	pathogenic	-0.255	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
R/G	0.9082	likely_pathogenic	0.892	pathogenic	-0.186	Destabilizing	1.0	D	0.634	neutral	N	0.486838196	None	None	I
R/H	0.3643	ambiguous	0.376	ambiguous	-0.682	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
R/I	0.8454	likely_pathogenic	0.8627	pathogenic	0.428	Stabilizing	1.0	D	0.743	deleterious	N	0.472239433	None	None	I
R/K	0.332	likely_benign	0.3405	ambiguous	-0.093	Destabilizing	0.997	D	0.595	neutral	N	0.512235115	None	None	I
R/L	0.8205	likely_pathogenic	0.8357	pathogenic	0.428	Stabilizing	1.0	D	0.634	neutral	None	None	None	None	I
R/M	0.8997	likely_pathogenic	0.9037	pathogenic	0.056	Stabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	I
R/N	0.974	likely_pathogenic	0.9729	pathogenic	0.152	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
R/P	0.9584	likely_pathogenic	0.9623	pathogenic	0.303	Stabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
R/Q	0.353	ambiguous	0.3533	ambiguous	0.041	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
R/S	0.9694	likely_pathogenic	0.9682	pathogenic	-0.154	Destabilizing	1.0	D	0.689	prob.neutral	N	0.463845642	None	None	I
R/T	0.938	likely_pathogenic	0.9384	pathogenic	0.021	Stabilizing	1.0	D	0.682	prob.neutral	N	0.476354037	None	None	I
R/V	0.9048	likely_pathogenic	0.9154	pathogenic	0.303	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
R/W	0.633	likely_pathogenic	0.6414	pathogenic	-0.336	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
R/Y	0.8768	likely_pathogenic	0.8824	pathogenic	0.069	Stabilizing	1.0	D	0.73	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.