TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23730	71413;71414;71415	chr2:178574944;178574943;178574942	chr2:179439671;179439670;179439669
N2AB	22089	66490;66491;66492	chr2:178574944;178574943;178574942	chr2:179439671;179439670;179439669
N2A	21162	63709;63710;63711	chr2:178574944;178574943;178574942	chr2:179439671;179439670;179439669
N2B	14665	44218;44219;44220	chr2:178574944;178574943;178574942	chr2:179439671;179439670;179439669
Novex-1	14790	44593;44594;44595	chr2:178574944;178574943;178574942	chr2:179439671;179439670;179439669
Novex-2	14857	44794;44795;44796	chr2:178574944;178574943;178574942	chr2:179439671;179439670;179439669
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: Fn3-60
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.1677
• 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	0.902	0.73	0.717430608715	gnomAD-4.0.0	1.36901E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.7993E-06	0	0
P/T	rs1709530947	None	1.0	D	0.89	0.71	0.735346534977	gnomAD-4.0.0	6.84504E-07	None	None	None	None	N	None	0	2.23814E-05	None	0	0	None	0	0	0	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	0.7014	likely_pathogenic	0.6459	pathogenic	-2.425	Highly Destabilizing	1.0	D	0.828	deleterious	D	0.586529616	None	None	N
P/C	0.9317	likely_pathogenic	0.9145	pathogenic	-2.093	Highly Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
P/D	0.9996	likely_pathogenic	0.9994	pathogenic	-3.461	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
P/E	0.9983	likely_pathogenic	0.9972	pathogenic	-3.209	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
P/F	0.999	likely_pathogenic	0.9985	pathogenic	-1.328	Destabilizing	1.0	D	0.933	deleterious	None	None	None	None	N
P/G	0.9927	likely_pathogenic	0.9901	pathogenic	-2.969	Highly Destabilizing	1.0	D	0.93	deleterious	None	None	None	None	N
P/H	0.9981	likely_pathogenic	0.9973	pathogenic	-2.771	Highly Destabilizing	1.0	D	0.896	deleterious	D	0.628692501	None	None	N
P/I	0.8393	likely_pathogenic	0.8096	pathogenic	-0.87	Destabilizing	1.0	D	0.941	deleterious	None	None	None	None	N
P/K	0.9988	likely_pathogenic	0.9982	pathogenic	-2.133	Highly Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
P/L	0.8782	likely_pathogenic	0.8479	pathogenic	-0.87	Destabilizing	1.0	D	0.927	deleterious	D	0.628288893	None	None	N
P/M	0.9752	likely_pathogenic	0.9682	pathogenic	-1.105	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
P/N	0.9988	likely_pathogenic	0.9982	pathogenic	-2.595	Highly Destabilizing	1.0	D	0.943	deleterious	None	None	None	None	N
P/Q	0.9961	likely_pathogenic	0.9936	pathogenic	-2.367	Highly Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	N
P/R	0.9964	likely_pathogenic	0.9944	pathogenic	-1.974	Destabilizing	1.0	D	0.945	deleterious	D	0.628490697	None	None	N
P/S	0.9774	likely_pathogenic	0.9652	pathogenic	-3.124	Highly Destabilizing	1.0	D	0.902	deleterious	D	0.628288893	None	None	N
P/T	0.9294	likely_pathogenic	0.9061	pathogenic	-2.74	Highly Destabilizing	1.0	D	0.89	deleterious	D	0.612239171	None	None	N
P/V	0.6012	likely_pathogenic	0.57	pathogenic	-1.367	Destabilizing	1.0	D	0.93	deleterious	None	None	None	None	N
P/W	0.9999	likely_pathogenic	0.9998	pathogenic	-1.953	Destabilizing	1.0	D	0.91	deleterious	None	None	None	None	N
P/Y	0.9996	likely_pathogenic	0.9994	pathogenic	-1.638	Destabilizing	1.0	D	0.938	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.