TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34387	103384;103385;103386	chr2:178533456;178533455;178533454	chr2:179398183;179398182;179398181
N2AB	32746	98461;98462;98463	chr2:178533456;178533455;178533454	chr2:179398183;179398182;179398181
N2A	31819	95680;95681;95682	chr2:178533456;178533455;178533454	chr2:179398183;179398182;179398181
N2B	25322	76189;76190;76191	chr2:178533456;178533455;178533454	chr2:179398183;179398182;179398181
Novex-1	25447	76564;76565;76566	chr2:178533456;178533455;178533454	chr2:179398183;179398182;179398181
Novex-2	25514	76765;76766;76767	chr2:178533456;178533455;178533454	chr2:179398183;179398182;179398181
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-162
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.4037
• 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
S/P	None	None	0.999	N	0.665	0.591	0.491387584038	gnomAD-4.0.0	1.59145E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43287E-05	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
S/A	0.1948	likely_benign	0.1625	benign	-0.564	Destabilizing	0.987	D	0.341	neutral	N	0.475704751	None	None	N
S/C	0.3965	ambiguous	0.3411	ambiguous	-0.34	Destabilizing	1.0	D	0.641	neutral	N	0.487773606	None	None	N
S/D	0.911	likely_pathogenic	0.8647	pathogenic	-0.333	Destabilizing	1.0	D	0.553	neutral	None	None	None	None	N
S/E	0.9305	likely_pathogenic	0.8893	pathogenic	-0.334	Destabilizing	0.999	D	0.515	neutral	None	None	None	None	N
S/F	0.7046	likely_pathogenic	0.5728	pathogenic	-0.657	Destabilizing	0.997	D	0.682	prob.neutral	N	0.506451733	None	None	N
S/G	0.3628	ambiguous	0.3086	benign	-0.83	Destabilizing	0.999	D	0.411	neutral	None	None	None	None	N
S/H	0.8248	likely_pathogenic	0.7604	pathogenic	-1.328	Destabilizing	1.0	D	0.635	neutral	None	None	None	None	N
S/I	0.6666	likely_pathogenic	0.539	ambiguous	0.036	Stabilizing	0.995	D	0.622	neutral	None	None	None	None	N
S/K	0.9762	likely_pathogenic	0.9552	pathogenic	-0.831	Destabilizing	0.999	D	0.489	neutral	None	None	None	None	N
S/L	0.351	ambiguous	0.2527	benign	0.036	Stabilizing	0.269	N	0.38	neutral	None	None	None	None	N
S/M	0.5169	ambiguous	0.428	ambiguous	0.249	Stabilizing	0.998	D	0.66	neutral	None	None	None	None	N
S/N	0.5882	likely_pathogenic	0.4798	ambiguous	-0.721	Destabilizing	1.0	D	0.534	neutral	None	None	None	None	N
S/P	0.9783	likely_pathogenic	0.9658	pathogenic	-0.129	Destabilizing	0.999	D	0.665	neutral	N	0.498787516	None	None	N
S/Q	0.8876	likely_pathogenic	0.844	pathogenic	-0.818	Destabilizing	1.0	D	0.576	neutral	None	None	None	None	N
S/R	0.9601	likely_pathogenic	0.928	pathogenic	-0.737	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
S/T	0.1714	likely_benign	0.1381	benign	-0.684	Destabilizing	0.994	D	0.407	neutral	N	0.442245539	None	None	N
S/V	0.6262	likely_pathogenic	0.5119	ambiguous	-0.129	Destabilizing	0.983	D	0.576	neutral	None	None	None	None	N
S/W	0.8077	likely_pathogenic	0.7434	pathogenic	-0.702	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
S/Y	0.6932	likely_pathogenic	0.572	pathogenic	-0.44	Destabilizing	0.999	D	0.695	prob.neutral	N	0.487266627	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.