TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17684	53275;53276;53277	chr2:178607638;178607637;178607636	chr2:179472365;179472364;179472363
N2AB	16043	48352;48353;48354	chr2:178607638;178607637;178607636	chr2:179472365;179472364;179472363
N2A	15116	45571;45572;45573	chr2:178607638;178607637;178607636	chr2:179472365;179472364;179472363
N2B	8619	26080;26081;26082	chr2:178607638;178607637;178607636	chr2:179472365;179472364;179472363
Novex-1	8744	26455;26456;26457	chr2:178607638;178607637;178607636	chr2:179472365;179472364;179472363
Novex-2	8811	26656;26657;26658	chr2:178607638;178607637;178607636	chr2:179472365;179472364;179472363
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-113
• Domain position: 8
• Structural Position: 16
• Q(SASA): 0.1181
• 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
I/V	rs1456939827	None	0.011	N	0.179	0.099	0.602985972322	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	3.88954E-04	None	0	0	0	0	0
I/V	rs1456939827	None	0.011	N	0.179	0.099	0.602985972322	gnomAD-4.0.0	8.05967E-06	None	None	None	None	N	None	0	0	None	0	2.90438E-04	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
I/A	0.8786	likely_pathogenic	0.8471	pathogenic	-2.115	Highly Destabilizing	0.702	D	0.528	neutral	None	None	None	None	N
I/C	0.8861	likely_pathogenic	0.8462	pathogenic	-1.287	Destabilizing	0.999	D	0.583	neutral	None	None	None	None	N
I/D	0.9876	likely_pathogenic	0.9882	pathogenic	-1.873	Destabilizing	0.988	D	0.655	neutral	None	None	None	None	N
I/E	0.9586	likely_pathogenic	0.9616	pathogenic	-1.761	Destabilizing	0.988	D	0.645	neutral	None	None	None	None	N
I/F	0.4563	ambiguous	0.4504	ambiguous	-1.301	Destabilizing	0.988	D	0.589	neutral	None	None	None	None	N
I/G	0.9665	likely_pathogenic	0.9612	pathogenic	-2.556	Highly Destabilizing	0.988	D	0.643	neutral	None	None	None	None	N
I/H	0.9589	likely_pathogenic	0.9578	pathogenic	-1.873	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	N
I/K	0.9223	likely_pathogenic	0.9311	pathogenic	-1.606	Destabilizing	0.984	D	0.645	neutral	N	0.491977115	None	None	N
I/L	0.2174	likely_benign	0.2152	benign	-0.907	Destabilizing	0.437	N	0.41	neutral	N	0.478224982	None	None	N
I/M	0.2243	likely_benign	0.2097	benign	-0.708	Destabilizing	0.984	D	0.551	neutral	N	0.491470136	None	None	N
I/N	0.892	likely_pathogenic	0.8894	pathogenic	-1.612	Destabilizing	0.988	D	0.66	neutral	None	None	None	None	N
I/P	0.9932	likely_pathogenic	0.9938	pathogenic	-1.283	Destabilizing	0.996	D	0.66	neutral	None	None	None	None	N
I/Q	0.9314	likely_pathogenic	0.9293	pathogenic	-1.645	Destabilizing	0.996	D	0.671	neutral	None	None	None	None	N
I/R	0.902	likely_pathogenic	0.9092	pathogenic	-1.127	Destabilizing	0.984	D	0.66	neutral	N	0.486127765	None	None	N
I/S	0.9147	likely_pathogenic	0.8992	pathogenic	-2.286	Highly Destabilizing	0.851	D	0.569	neutral	None	None	None	None	N
I/T	0.805	likely_pathogenic	0.7605	pathogenic	-2.049	Highly Destabilizing	0.103	N	0.387	neutral	D	0.52882716	None	None	N
I/V	0.1153	likely_benign	0.0987	benign	-1.283	Destabilizing	0.011	N	0.179	neutral	N	0.390427065	None	None	N
I/W	0.9654	likely_pathogenic	0.9669	pathogenic	-1.555	Destabilizing	0.999	D	0.631	neutral	None	None	None	None	N
I/Y	0.8701	likely_pathogenic	0.8754	pathogenic	-1.289	Destabilizing	0.996	D	0.627	neutral	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.