TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17824	53695;53696;53697	chr2:178607132;178607131;178607130	chr2:179471859;179471858;179471857
N2AB	16183	48772;48773;48774	chr2:178607132;178607131;178607130	chr2:179471859;179471858;179471857
N2A	15256	45991;45992;45993	chr2:178607132;178607131;178607130	chr2:179471859;179471858;179471857
N2B	8759	26500;26501;26502	chr2:178607132;178607131;178607130	chr2:179471859;179471858;179471857
Novex-1	8884	26875;26876;26877	chr2:178607132;178607131;178607130	chr2:179471859;179471858;179471857
Novex-2	8951	27076;27077;27078	chr2:178607132;178607131;178607130	chr2:179471859;179471858;179471857
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-17
• Domain position: 61
• Structural Position: 93
• Q(SASA): 0.0998
• 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	rs765709539	-3.012	0.99	N	0.73	0.455	0.669809909516	gnomAD-2.1.1	3.63E-05	None	None	None	None	N	None	0	0	None	0	0	None	2.61986E-04	None	0	8.91E-06	0
I/T	rs765709539	-3.012	0.99	N	0.73	0.455	0.669809909516	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07383E-04	0
I/T	rs765709539	-3.012	0.99	N	0.73	0.455	0.669809909516	gnomAD-4.0.0	1.17809E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.47968E-07	1.97824E-04	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	0.9625	likely_pathogenic	0.969	pathogenic	-2.608	Highly Destabilizing	0.964	D	0.703	prob.neutral	None	None	None	None	N
I/C	0.9461	likely_pathogenic	0.9497	pathogenic	-1.862	Destabilizing	0.171	N	0.479	neutral	None	None	None	None	N
I/D	0.9981	likely_pathogenic	0.9984	pathogenic	-2.992	Highly Destabilizing	0.999	D	0.814	deleterious	None	None	None	None	N
I/E	0.9951	likely_pathogenic	0.9956	pathogenic	-2.753	Highly Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
I/F	0.7571	likely_pathogenic	0.7539	pathogenic	-1.623	Destabilizing	0.999	D	0.733	prob.delet.	N	0.471395238	None	None	N
I/G	0.9964	likely_pathogenic	0.9967	pathogenic	-3.176	Highly Destabilizing	0.998	D	0.805	deleterious	None	None	None	None	N
I/H	0.9944	likely_pathogenic	0.9948	pathogenic	-2.706	Highly Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
I/K	0.993	likely_pathogenic	0.9932	pathogenic	-2.065	Highly Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
I/L	0.4278	ambiguous	0.446	ambiguous	-0.958	Destabilizing	0.953	D	0.46	neutral	N	0.491905489	None	None	N
I/M	0.4768	ambiguous	0.4773	ambiguous	-0.831	Destabilizing	0.999	D	0.689	prob.neutral	N	0.477159364	None	None	N
I/N	0.9794	likely_pathogenic	0.981	pathogenic	-2.438	Highly Destabilizing	0.999	D	0.808	deleterious	N	0.507126903	None	None	N
I/P	0.9963	likely_pathogenic	0.9963	pathogenic	-1.49	Destabilizing	0.999	D	0.804	deleterious	None	None	None	None	N
I/Q	0.993	likely_pathogenic	0.9935	pathogenic	-2.274	Highly Destabilizing	0.999	D	0.835	deleterious	None	None	None	None	N
I/R	0.9899	likely_pathogenic	0.9906	pathogenic	-1.811	Destabilizing	0.999	D	0.806	deleterious	None	None	None	None	N
I/S	0.9782	likely_pathogenic	0.9808	pathogenic	-3.13	Highly Destabilizing	0.997	D	0.753	deleterious	N	0.477159364	None	None	N
I/T	0.9537	likely_pathogenic	0.9519	pathogenic	-2.736	Highly Destabilizing	0.99	D	0.73	prob.delet.	N	0.480375368	None	None	N
I/V	0.1316	likely_benign	0.1259	benign	-1.49	Destabilizing	0.953	D	0.465	neutral	N	0.409636396	None	None	N
I/W	0.9947	likely_pathogenic	0.9944	pathogenic	-2.062	Highly Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
I/Y	0.9753	likely_pathogenic	0.9772	pathogenic	-1.76	Destabilizing	0.999	D	0.725	prob.delet.	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.