TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18200	54823;54824;54825	chr2:178604089;178604088;178604087	chr2:179468816;179468815;179468814
N2AB	16559	49900;49901;49902	chr2:178604089;178604088;178604087	chr2:179468816;179468815;179468814
N2A	15632	47119;47120;47121	chr2:178604089;178604088;178604087	chr2:179468816;179468815;179468814
N2B	9135	27628;27629;27630	chr2:178604089;178604088;178604087	chr2:179468816;179468815;179468814
Novex-1	9260	28003;28004;28005	chr2:178604089;178604088;178604087	chr2:179468816;179468815;179468814
Novex-2	9327	28204;28205;28206	chr2:178604089;178604088;178604087	chr2:179468816;179468815;179468814
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-20
• Domain position: 35
• Structural Position: 37
• Q(SASA): 0.0681
• 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
G/D	None	None	1.0	N	0.849	0.599	0.500050830518	gnomAD-4.0.0	1.59345E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43443E-05	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
G/A	0.5435	ambiguous	0.4811	ambiguous	-0.434	Destabilizing	1.0	D	0.666	neutral	N	0.485441477	None	None	N
G/C	0.8448	likely_pathogenic	0.8142	pathogenic	-0.594	Destabilizing	1.0	D	0.816	deleterious	N	0.50021805	None	None	N
G/D	0.96	likely_pathogenic	0.946	pathogenic	-1.506	Destabilizing	1.0	D	0.849	deleterious	N	0.490961659	None	None	N
G/E	0.9685	likely_pathogenic	0.9561	pathogenic	-1.401	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
G/F	0.9897	likely_pathogenic	0.9827	pathogenic	-0.526	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
G/H	0.9687	likely_pathogenic	0.9622	pathogenic	-1.606	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
G/I	0.9887	likely_pathogenic	0.9786	pathogenic	0.46	Stabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
G/K	0.9902	likely_pathogenic	0.9849	pathogenic	-0.947	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
G/L	0.9839	likely_pathogenic	0.9735	pathogenic	0.46	Stabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
G/M	0.9834	likely_pathogenic	0.9762	pathogenic	0.306	Stabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
G/N	0.8963	likely_pathogenic	0.8993	pathogenic	-0.971	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
G/P	0.9996	likely_pathogenic	0.9992	pathogenic	0.208	Stabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
G/Q	0.9556	likely_pathogenic	0.9423	pathogenic	-0.879	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
G/R	0.9673	likely_pathogenic	0.9496	pathogenic	-1.031	Destabilizing	1.0	D	0.883	deleterious	N	0.484427519	None	None	N
G/S	0.4604	ambiguous	0.4137	ambiguous	-1.273	Destabilizing	1.0	D	0.713	prob.delet.	D	0.525314347	None	None	N
G/T	0.8942	likely_pathogenic	0.8515	pathogenic	-1.063	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
G/V	0.9696	likely_pathogenic	0.9458	pathogenic	0.208	Stabilizing	1.0	D	0.901	deleterious	D	0.525448649	None	None	N
G/W	0.9816	likely_pathogenic	0.9714	pathogenic	-1.307	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
G/Y	0.9642	likely_pathogenic	0.9528	pathogenic	-0.663	Destabilizing	1.0	D	0.862	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.