TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16073	48442;48443;48444	chr2:178616574;178616573;178616572	chr2:179481301;179481300;179481299
N2AB	14432	43519;43520;43521	chr2:178616574;178616573;178616572	chr2:179481301;179481300;179481299
N2A	13505	40738;40739;40740	chr2:178616574;178616573;178616572	chr2:179481301;179481300;179481299
N2B	7008	21247;21248;21249	chr2:178616574;178616573;178616572	chr2:179481301;179481300;179481299
Novex-1	7133	21622;21623;21624	chr2:178616574;178616573;178616572	chr2:179481301;179481300;179481299
Novex-2	7200	21823;21824;21825	chr2:178616574;178616573;178616572	chr2:179481301;179481300;179481299
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-4
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.2994
• 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
H/R	None	None	0.968	N	0.477	0.33	0.293502639404	gnomAD-4.0.0	1.59406E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43394E-05	0
H/Y	rs1343135130	0.428	0.982	N	0.471	0.287	0.329282125956	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.47E-05	0	None	0	0	None	0	None	0	0	0
H/Y	rs1343135130	0.428	0.982	N	0.471	0.287	0.329282125956	gnomAD-4.0.0	1.59414E-06	None	None	None	None	N	None	5.68117E-05	0	None	0	0	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
H/A	0.3039	likely_benign	0.3353	benign	-1.043	Destabilizing	0.919	D	0.557	neutral	None	None	None	None	N
H/C	0.1472	likely_benign	0.1719	benign	-0.412	Destabilizing	0.999	D	0.772	deleterious	None	None	None	None	N
H/D	0.3581	ambiguous	0.3567	ambiguous	-0.594	Destabilizing	0.811	D	0.492	neutral	N	0.469057285	None	None	N
H/E	0.3436	ambiguous	0.3631	ambiguous	-0.515	Destabilizing	0.919	D	0.397	neutral	None	None	None	None	N
H/F	0.254	likely_benign	0.3045	benign	-0.198	Destabilizing	0.996	D	0.641	neutral	None	None	None	None	N
H/G	0.4039	ambiguous	0.4304	ambiguous	-1.373	Destabilizing	0.851	D	0.542	neutral	None	None	None	None	N
H/I	0.2435	likely_benign	0.272	benign	-0.142	Destabilizing	0.996	D	0.783	deleterious	None	None	None	None	N
H/K	0.2345	likely_benign	0.241	benign	-0.884	Destabilizing	0.919	D	0.506	neutral	None	None	None	None	N
H/L	0.1119	likely_benign	0.1238	benign	-0.142	Destabilizing	0.984	D	0.691	prob.neutral	N	0.459827469	None	None	N
H/M	0.3585	ambiguous	0.4124	ambiguous	-0.248	Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	N
H/N	0.1323	likely_benign	0.1408	benign	-0.824	Destabilizing	0.026	N	0.325	neutral	N	0.42007307	None	None	N
H/P	0.637	likely_pathogenic	0.6171	pathogenic	-0.423	Destabilizing	0.995	D	0.695	prob.neutral	N	0.496722455	None	None	N
H/Q	0.165	likely_benign	0.1727	benign	-0.651	Destabilizing	0.984	D	0.483	neutral	N	0.410353436	None	None	N
H/R	0.1097	likely_benign	0.1102	benign	-1.075	Destabilizing	0.968	D	0.477	neutral	N	0.467041343	None	None	N
H/S	0.2342	likely_benign	0.2556	benign	-0.995	Destabilizing	0.851	D	0.459	neutral	None	None	None	None	N
H/T	0.2104	likely_benign	0.231	benign	-0.82	Destabilizing	0.976	D	0.621	neutral	None	None	None	None	N
H/V	0.2085	likely_benign	0.2354	benign	-0.423	Destabilizing	0.988	D	0.741	deleterious	None	None	None	None	N
H/W	0.3917	ambiguous	0.419	ambiguous	0.047	Stabilizing	0.999	D	0.694	prob.neutral	None	None	None	None	N
H/Y	0.1059	likely_benign	0.1174	benign	0.271	Stabilizing	0.982	D	0.471	neutral	N	0.478377791	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.