TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22650	68173;68174;68175	chr2:178579082;178579081;178579080	chr2:179443809;179443808;179443807
N2AB	21009	63250;63251;63252	chr2:178579082;178579081;178579080	chr2:179443809;179443808;179443807
N2A	20082	60469;60470;60471	chr2:178579082;178579081;178579080	chr2:179443809;179443808;179443807
N2B	13585	40978;40979;40980	chr2:178579082;178579081;178579080	chr2:179443809;179443808;179443807
Novex-1	13710	41353;41354;41355	chr2:178579082;178579081;178579080	chr2:179443809;179443808;179443807
Novex-2	13777	41554;41555;41556	chr2:178579082;178579081;178579080	chr2:179443809;179443808;179443807
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: Fn3-52
• Domain position: 8
• Structural Position: 8
• Q(SASA): 0.5644
• 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	N	0.814	0.439	0.37568098594	gnomAD-4.0.0	2.05315E-06	None	None	None	None	N	None	0	6.71141E-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	0.3241	likely_benign	0.3014	benign	-0.481	Destabilizing	1.0	D	0.781	deleterious	N	0.483485559	None	None	N
P/C	0.8273	likely_pathogenic	0.7946	pathogenic	-0.817	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
P/D	0.7121	likely_pathogenic	0.6941	pathogenic	-0.329	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
P/E	0.6037	likely_pathogenic	0.5668	pathogenic	-0.425	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
P/F	0.8788	likely_pathogenic	0.842	pathogenic	-0.625	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
P/G	0.702	likely_pathogenic	0.682	pathogenic	-0.604	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
P/H	0.5634	ambiguous	0.522	ambiguous	-0.055	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
P/I	0.6908	likely_pathogenic	0.6348	pathogenic	-0.299	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
P/K	0.656	likely_pathogenic	0.6136	pathogenic	-0.528	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
P/L	0.4267	ambiguous	0.3751	ambiguous	-0.299	Destabilizing	1.0	D	0.832	deleterious	N	0.5118888	None	None	N
P/M	0.6744	likely_pathogenic	0.6251	pathogenic	-0.551	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
P/N	0.6471	likely_pathogenic	0.6241	pathogenic	-0.379	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
P/Q	0.5077	ambiguous	0.463	ambiguous	-0.578	Destabilizing	1.0	D	0.802	deleterious	N	0.48663911	None	None	N
P/R	0.5438	ambiguous	0.5098	ambiguous	-0.023	Destabilizing	1.0	D	0.836	deleterious	N	0.484246027	None	None	N
P/S	0.4692	ambiguous	0.449	ambiguous	-0.728	Destabilizing	1.0	D	0.814	deleterious	N	0.482017528	None	None	N
P/T	0.3434	ambiguous	0.3198	benign	-0.723	Destabilizing	1.0	D	0.811	deleterious	N	0.474775826	None	None	N
P/V	0.5532	ambiguous	0.5105	ambiguous	-0.328	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
P/W	0.9414	likely_pathogenic	0.9279	pathogenic	-0.696	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
P/Y	0.8462	likely_pathogenic	0.8165	pathogenic	-0.421	Destabilizing	1.0	D	0.817	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.