TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32604	98035;98036;98037	chr2:178540356;178540355;178540354	chr2:179405083;179405082;179405081
N2AB	30963	93112;93113;93114	chr2:178540356;178540355;178540354	chr2:179405083;179405082;179405081
N2A	30036	90331;90332;90333	chr2:178540356;178540355;178540354	chr2:179405083;179405082;179405081
N2B	23539	70840;70841;70842	chr2:178540356;178540355;178540354	chr2:179405083;179405082;179405081
Novex-1	23664	71215;71216;71217	chr2:178540356;178540355;178540354	chr2:179405083;179405082;179405081
Novex-2	23731	71416;71417;71418	chr2:178540356;178540355;178540354	chr2:179405083;179405082;179405081
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-126
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.1046
• 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/S	None	None	1.0	D	0.885	0.657	0.61510976853	gnomAD-4.0.0	2.4007E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62506E-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
P/A	0.7594	likely_pathogenic	0.7595	pathogenic	-2.315	Highly Destabilizing	1.0	D	0.841	deleterious	D	0.532788116	None	None	N
P/C	0.9615	likely_pathogenic	0.9551	pathogenic	-2.238	Highly Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
P/D	0.9985	likely_pathogenic	0.9982	pathogenic	-3.425	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
P/E	0.9961	likely_pathogenic	0.9957	pathogenic	-3.191	Highly Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
P/F	0.9966	likely_pathogenic	0.9963	pathogenic	-1.119	Destabilizing	1.0	D	0.932	deleterious	None	None	None	None	N
P/G	0.9846	likely_pathogenic	0.9845	pathogenic	-2.825	Highly Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
P/H	0.9953	likely_pathogenic	0.9955	pathogenic	-2.495	Highly Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
P/I	0.8841	likely_pathogenic	0.8567	pathogenic	-0.864	Destabilizing	1.0	D	0.94	deleterious	None	None	None	None	N
P/K	0.9974	likely_pathogenic	0.9974	pathogenic	-1.896	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
P/L	0.835	likely_pathogenic	0.8153	pathogenic	-0.864	Destabilizing	1.0	D	0.924	deleterious	D	0.564121554	None	None	N
P/M	0.9693	likely_pathogenic	0.9641	pathogenic	-1.308	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
P/N	0.9971	likely_pathogenic	0.9966	pathogenic	-2.379	Highly Destabilizing	1.0	D	0.94	deleterious	None	None	None	None	N
P/Q	0.9927	likely_pathogenic	0.9926	pathogenic	-2.17	Highly Destabilizing	1.0	D	0.902	deleterious	D	0.577252286	None	None	N
P/R	0.9931	likely_pathogenic	0.9934	pathogenic	-1.766	Destabilizing	1.0	D	0.941	deleterious	D	0.576745307	None	None	N
P/S	0.9766	likely_pathogenic	0.9765	pathogenic	-2.878	Highly Destabilizing	1.0	D	0.885	deleterious	D	0.558894542	None	None	N
P/T	0.9252	likely_pathogenic	0.9213	pathogenic	-2.514	Highly Destabilizing	1.0	D	0.877	deleterious	D	0.576238328	None	None	N
P/V	0.7724	likely_pathogenic	0.7327	pathogenic	-1.327	Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
P/W	0.9992	likely_pathogenic	0.9993	pathogenic	-1.677	Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
P/Y	0.9981	likely_pathogenic	0.9979	pathogenic	-1.415	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.