TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29537	88834;88835;88836	chr2:178554738;178554737;178554736	chr2:179419465;179419464;179419463
N2AB	27896	83911;83912;83913	chr2:178554738;178554737;178554736	chr2:179419465;179419464;179419463
N2A	26969	81130;81131;81132	chr2:178554738;178554737;178554736	chr2:179419465;179419464;179419463
N2B	20472	61639;61640;61641	chr2:178554738;178554737;178554736	chr2:179419465;179419464;179419463
Novex-1	20597	62014;62015;62016	chr2:178554738;178554737;178554736	chr2:179419465;179419464;179419463
Novex-2	20664	62215;62216;62217	chr2:178554738;178554737;178554736	chr2:179419465;179419464;179419463
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-103
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.1259
• 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
P/R	rs1482625198	-1.768	0.999	D	0.907	0.659	0.892145347143	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	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
P/A	0.2417	likely_benign	0.2712	benign	-2.217	Highly Destabilizing	0.992	D	0.798	deleterious	D	0.576082206	None	None	N
P/C	0.6541	likely_pathogenic	0.7268	pathogenic	-1.908	Destabilizing	1.0	D	0.922	deleterious	None	None	None	None	N
P/D	0.9945	likely_pathogenic	0.9959	pathogenic	-3.266	Highly Destabilizing	0.999	D	0.86	deleterious	None	None	None	None	N
P/E	0.9804	likely_pathogenic	0.9845	pathogenic	-3.023	Highly Destabilizing	0.999	D	0.851	deleterious	None	None	None	None	N
P/F	0.9879	likely_pathogenic	0.992	pathogenic	-1.187	Destabilizing	1.0	D	0.936	deleterious	None	None	None	None	N
P/G	0.934	likely_pathogenic	0.9481	pathogenic	-2.762	Highly Destabilizing	0.997	D	0.861	deleterious	None	None	None	None	N
P/H	0.9791	likely_pathogenic	0.9847	pathogenic	-2.573	Highly Destabilizing	1.0	D	0.915	deleterious	D	0.627763843	None	None	N
P/I	0.5474	ambiguous	0.643	pathogenic	-0.671	Destabilizing	1.0	D	0.916	deleterious	None	None	None	None	N
P/K	0.991	likely_pathogenic	0.9936	pathogenic	-1.88	Destabilizing	0.999	D	0.857	deleterious	None	None	None	None	N
P/L	0.5781	likely_pathogenic	0.6668	pathogenic	-0.671	Destabilizing	0.999	D	0.913	deleterious	D	0.595321512	None	None	N
P/M	0.8714	likely_pathogenic	0.9077	pathogenic	-0.922	Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
P/N	0.9863	likely_pathogenic	0.9897	pathogenic	-2.322	Highly Destabilizing	0.999	D	0.899	deleterious	None	None	None	None	N
P/Q	0.9632	likely_pathogenic	0.9724	pathogenic	-2.116	Highly Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
P/R	0.9732	likely_pathogenic	0.9806	pathogenic	-1.75	Destabilizing	0.999	D	0.907	deleterious	D	0.627562038	None	None	N
P/S	0.7193	likely_pathogenic	0.7548	pathogenic	-2.857	Highly Destabilizing	0.957	D	0.702	prob.neutral	D	0.601822122	None	None	N
P/T	0.5212	ambiguous	0.5781	pathogenic	-2.479	Highly Destabilizing	0.998	D	0.831	deleterious	D	0.611542677	None	None	N
P/V	0.2957	likely_benign	0.3495	ambiguous	-1.163	Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
P/W	0.9978	likely_pathogenic	0.9985	pathogenic	-1.803	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
P/Y	0.9951	likely_pathogenic	0.9966	pathogenic	-1.449	Destabilizing	1.0	D	0.937	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.