TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6587	19984;19985;19986	chr2:178727819;178727818;178727817	chr2:179592546;179592545;179592544
N2AB	6270	19033;19034;19035	chr2:178727819;178727818;178727817	chr2:179592546;179592545;179592544
N2A	5343	16252;16253;16254	chr2:178727819;178727818;178727817	chr2:179592546;179592545;179592544
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-50
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.4618
• 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	rs2079621657	None	0.999	N	0.75	0.383	0.330589388543	gnomAD-4.0.0	1.60498E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.46011E-05	0
P/T	None	None	0.999	N	0.709	0.332	0.263612267334	gnomAD-4.0.0	6.86684E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.01634E-07	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	0.1282	likely_benign	0.1272	benign	-0.75	Destabilizing	0.996	D	0.596	neutral	N	0.471116424	None	None	N
P/C	0.7567	likely_pathogenic	0.765	pathogenic	-0.603	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
P/D	0.8535	likely_pathogenic	0.8606	pathogenic	-0.323	Destabilizing	0.994	D	0.677	prob.neutral	None	None	None	None	N
P/E	0.538	ambiguous	0.5495	ambiguous	-0.419	Destabilizing	0.91	D	0.387	neutral	None	None	None	None	N
P/F	0.7351	likely_pathogenic	0.7363	pathogenic	-0.86	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
P/G	0.5815	likely_pathogenic	0.5848	pathogenic	-0.936	Destabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	N
P/H	0.4596	ambiguous	0.4445	ambiguous	-0.491	Destabilizing	1.0	D	0.745	deleterious	N	0.477239409	None	None	N
P/I	0.4266	ambiguous	0.4166	ambiguous	-0.395	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
P/K	0.5198	ambiguous	0.5313	ambiguous	-0.527	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
P/L	0.1638	likely_benign	0.154	benign	-0.395	Destabilizing	0.999	D	0.737	prob.delet.	N	0.49676423	None	None	N
P/M	0.4992	ambiguous	0.4976	ambiguous	-0.285	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
P/N	0.7272	likely_pathogenic	0.729	pathogenic	-0.203	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
P/Q	0.3276	likely_benign	0.3145	benign	-0.463	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
P/R	0.3117	likely_benign	0.3113	benign	0.001	Stabilizing	0.999	D	0.75	deleterious	N	0.461248295	None	None	N
P/S	0.2899	likely_benign	0.2869	benign	-0.655	Destabilizing	0.999	D	0.691	prob.neutral	N	0.50471171	None	None	N
P/T	0.2025	likely_benign	0.2007	benign	-0.647	Destabilizing	0.999	D	0.709	prob.delet.	N	0.498073739	None	None	N
P/V	0.305	likely_benign	0.3049	benign	-0.477	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
P/W	0.8452	likely_pathogenic	0.8473	pathogenic	-0.935	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
P/Y	0.7282	likely_pathogenic	0.7362	pathogenic	-0.632	Destabilizing	1.0	D	0.768	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.