TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17848	53767;53768;53769	chr2:178607060;178607059;178607058	chr2:179471787;179471786;179471785
N2AB	16207	48844;48845;48846	chr2:178607060;178607059;178607058	chr2:179471787;179471786;179471785
N2A	15280	46063;46064;46065	chr2:178607060;178607059;178607058	chr2:179471787;179471786;179471785
N2B	8783	26572;26573;26574	chr2:178607060;178607059;178607058	chr2:179471787;179471786;179471785
Novex-1	8908	26947;26948;26949	chr2:178607060;178607059;178607058	chr2:179471787;179471786;179471785
Novex-2	8975	27148;27149;27150	chr2:178607060;178607059;178607058	chr2:179471787;179471786;179471785
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: Fn3-17
• Domain position: 85
• Structural Position: 120
• Q(SASA): 0.3223
• 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/T	None	None	0.993	N	0.74	0.382	0.517047913619	gnomAD-4.0.0	4.79528E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00059E-07	0	9.95388E-05

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	0.0884	likely_benign	0.0717	benign	-1.16	Destabilizing	0.117	N	0.451	neutral	N	0.472303383	None	None	N
P/C	0.6897	likely_pathogenic	0.6684	pathogenic	-0.787	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
P/D	0.9147	likely_pathogenic	0.8946	pathogenic	-1.04	Destabilizing	0.998	D	0.815	deleterious	None	None	None	None	N
P/E	0.7748	likely_pathogenic	0.7199	pathogenic	-1.096	Destabilizing	0.995	D	0.791	deleterious	None	None	None	None	N
P/F	0.8068	likely_pathogenic	0.7143	pathogenic	-0.989	Destabilizing	0.999	D	0.843	deleterious	None	None	None	None	N
P/G	0.5916	likely_pathogenic	0.5364	ambiguous	-1.393	Destabilizing	0.966	D	0.742	deleterious	None	None	None	None	N
P/H	0.6757	likely_pathogenic	0.5676	pathogenic	-0.856	Destabilizing	1.0	D	0.824	deleterious	N	0.521415589	None	None	N
P/I	0.7415	likely_pathogenic	0.6531	pathogenic	-0.651	Destabilizing	0.995	D	0.837	deleterious	None	None	None	None	N
P/K	0.8925	likely_pathogenic	0.8513	pathogenic	-1.092	Destabilizing	0.995	D	0.811	deleterious	None	None	None	None	N
P/L	0.5118	ambiguous	0.413	ambiguous	-0.651	Destabilizing	0.993	D	0.778	deleterious	N	0.484900683	None	None	N
P/M	0.7073	likely_pathogenic	0.63	pathogenic	-0.543	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
P/N	0.8628	likely_pathogenic	0.8239	pathogenic	-0.832	Destabilizing	0.998	D	0.844	deleterious	None	None	None	None	N
P/Q	0.6554	likely_pathogenic	0.5552	ambiguous	-1.068	Destabilizing	0.998	D	0.849	deleterious	None	None	None	None	N
P/R	0.8051	likely_pathogenic	0.717	pathogenic	-0.466	Destabilizing	0.997	D	0.843	deleterious	N	0.520401631	None	None	N
P/S	0.3177	likely_benign	0.2476	benign	-1.233	Destabilizing	0.987	D	0.734	prob.delet.	N	0.496928551	None	None	N
P/T	0.3334	likely_benign	0.2704	benign	-1.194	Destabilizing	0.993	D	0.74	deleterious	N	0.52065512	None	None	N
P/V	0.5017	ambiguous	0.4208	ambiguous	-0.786	Destabilizing	0.99	D	0.745	deleterious	None	None	None	None	N
P/W	0.9353	likely_pathogenic	0.8953	pathogenic	-1.105	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
P/Y	0.8326	likely_pathogenic	0.7525	pathogenic	-0.849	Destabilizing	1.0	D	0.844	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.