TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27505	82738;82739;82740	chr2:178563619;178563618;178563617	chr2:179428346;179428345;179428344
N2AB	25864	77815;77816;77817	chr2:178563619;178563618;178563617	chr2:179428346;179428345;179428344
N2A	24937	75034;75035;75036	chr2:178563619;178563618;178563617	chr2:179428346;179428345;179428344
N2B	18440	55543;55544;55545	chr2:178563619;178563618;178563617	chr2:179428346;179428345;179428344
Novex-1	18565	55918;55919;55920	chr2:178563619;178563618;178563617	chr2:179428346;179428345;179428344
Novex-2	18632	56119;56120;56121	chr2:178563619;178563618;178563617	chr2:179428346;179428345;179428344
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-88
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.2714
• 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	rs1270467286	None	None	N	0.283	0.052	0.244539031024	gnomAD-4.0.0	3.60098E-06	None	None	None	None	N	None	1.26695E-04	0	None	0	0	None	0	6.17284E-04	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	0.5624	ambiguous	0.584	pathogenic	-2.279	Highly Destabilizing	0.157	N	0.674	neutral	None	None	None	None	N
I/C	0.5927	likely_pathogenic	0.5903	pathogenic	-1.324	Destabilizing	0.909	D	0.724	prob.delet.	None	None	None	None	N
I/D	0.8634	likely_pathogenic	0.8576	pathogenic	-2.315	Highly Destabilizing	0.726	D	0.767	deleterious	None	None	None	None	N
I/E	0.8012	likely_pathogenic	0.7766	pathogenic	-2.247	Highly Destabilizing	0.726	D	0.755	deleterious	None	None	None	None	N
I/F	0.1193	likely_benign	0.1189	benign	-1.514	Destabilizing	0.331	N	0.702	prob.neutral	N	0.467316633	None	None	N
I/G	0.8077	likely_pathogenic	0.8187	pathogenic	-2.674	Highly Destabilizing	0.726	D	0.743	deleterious	None	None	None	None	N
I/H	0.3533	ambiguous	0.3291	benign	-1.942	Destabilizing	0.832	D	0.777	deleterious	None	None	None	None	N
I/K	0.5592	ambiguous	0.5073	ambiguous	-1.82	Destabilizing	0.726	D	0.757	deleterious	None	None	None	None	N
I/L	0.1089	likely_benign	0.1163	benign	-1.209	Destabilizing	0.025	N	0.485	neutral	N	0.515150495	None	None	N
I/M	0.1497	likely_benign	0.1528	benign	-0.854	Destabilizing	0.497	N	0.719	prob.delet.	N	0.494575148	None	None	N
I/N	0.362	ambiguous	0.3461	ambiguous	-1.732	Destabilizing	0.667	D	0.78	deleterious	N	0.471796404	None	None	N
I/P	0.9791	likely_pathogenic	0.9801	pathogenic	-1.541	Destabilizing	0.89	D	0.782	deleterious	None	None	None	None	N
I/Q	0.5332	ambiguous	0.5005	ambiguous	-1.862	Destabilizing	0.726	D	0.788	deleterious	None	None	None	None	N
I/R	0.3692	ambiguous	0.3318	benign	-1.16	Destabilizing	0.726	D	0.785	deleterious	None	None	None	None	N
I/S	0.3941	ambiguous	0.4086	ambiguous	-2.314	Highly Destabilizing	0.497	N	0.716	prob.delet.	N	0.471187293	None	None	N
I/T	0.364	ambiguous	0.361	ambiguous	-2.139	Highly Destabilizing	0.124	N	0.713	prob.delet.	N	0.505645577	None	None	N
I/V	0.0877	likely_benign	0.0859	benign	-1.541	Destabilizing	None	N	0.283	neutral	N	0.454083394	None	None	N
I/W	0.6057	likely_pathogenic	0.6215	pathogenic	-1.736	Destabilizing	0.909	D	0.776	deleterious	None	None	None	None	N
I/Y	0.3141	likely_benign	0.3141	benign	-1.536	Destabilizing	0.003	N	0.531	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.