TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4942	15049;15050;15051	chr2:178735622;178735621;178735620	chr2:179600349;179600348;179600347
N2AB	4625	14098;14099;14100	chr2:178735622;178735621;178735620	chr2:179600349;179600348;179600347
N2A	3698	11317;11318;11319	chr2:178735622;178735621;178735620	chr2:179600349;179600348;179600347
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: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-32
• Domain position: 55
• Structural Position: 135
• Q(SASA): 0.2134
• 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/T	rs773235984	-1.308	0.549	N	0.525	0.307	0.603169182973	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
I/T	rs773235984	-1.308	0.549	N	0.525	0.307	0.603169182973	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
I/T	rs773235984	-1.308	0.549	N	0.525	0.307	0.603169182973	gnomAD-4.0.0	3.84408E-06	None	None	None	None	N	None	3.38215E-05	0	None	0	2.42825E-05	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	0.1651	likely_benign	0.1874	benign	-2.086	Highly Destabilizing	0.25	N	0.499	neutral	None	None	None	None	N
I/C	0.5903	likely_pathogenic	0.6177	pathogenic	-1.157	Destabilizing	0.977	D	0.562	neutral	None	None	None	None	N
I/D	0.5365	ambiguous	0.5849	pathogenic	-2.048	Highly Destabilizing	0.972	D	0.641	neutral	None	None	None	None	N
I/E	0.3652	ambiguous	0.4001	ambiguous	-1.993	Destabilizing	0.92	D	0.638	neutral	None	None	None	None	N
I/F	0.1153	likely_benign	0.1242	benign	-1.408	Destabilizing	0.85	D	0.492	neutral	None	None	None	None	N
I/G	0.4782	ambiguous	0.5231	ambiguous	-2.472	Highly Destabilizing	0.92	D	0.635	neutral	None	None	None	None	N
I/H	0.311	likely_benign	0.3363	benign	-1.825	Destabilizing	0.992	D	0.631	neutral	None	None	None	None	N
I/K	0.1821	likely_benign	0.1969	benign	-1.503	Destabilizing	0.896	D	0.638	neutral	N	0.50888965	None	None	N
I/L	0.1155	likely_benign	0.1192	benign	-1.051	Destabilizing	0.001	N	0.119	neutral	N	0.511894355	None	None	N
I/M	0.078	likely_benign	0.0791	benign	-0.748	Destabilizing	0.099	N	0.259	neutral	D	0.567317211	None	None	N
I/N	0.1771	likely_benign	0.1943	benign	-1.383	Destabilizing	0.972	D	0.641	neutral	None	None	None	None	N
I/P	0.8326	likely_pathogenic	0.8732	pathogenic	-1.37	Destabilizing	0.972	D	0.641	neutral	None	None	None	None	N
I/Q	0.2777	likely_benign	0.3011	benign	-1.52	Destabilizing	0.92	D	0.645	neutral	None	None	None	None	N
I/R	0.1322	likely_benign	0.1413	benign	-0.932	Destabilizing	0.896	D	0.639	neutral	N	0.502252575	None	None	N
I/S	0.1808	likely_benign	0.2005	benign	-1.971	Destabilizing	0.617	D	0.604	neutral	None	None	None	None	N
I/T	0.0824	likely_benign	0.0896	benign	-1.806	Destabilizing	0.549	D	0.525	neutral	N	0.490149982	None	None	N
I/V	0.0732	likely_benign	0.0749	benign	-1.37	Destabilizing	0.002	N	0.129	neutral	N	0.506025056	None	None	N
I/W	0.5536	ambiguous	0.5757	pathogenic	-1.628	Destabilizing	0.992	D	0.653	neutral	None	None	None	None	N
I/Y	0.3288	likely_benign	0.3414	ambiguous	-1.4	Destabilizing	0.92	D	0.585	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.