TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9580	28963;28964;28965	chr2:178709581;178709580;178709579	chr2:179574308;179574307;179574306
N2AB	9263	28012;28013;28014	chr2:178709581;178709580;178709579	chr2:179574308;179574307;179574306
N2A	8336	25231;25232;25233	chr2:178709581;178709580;178709579	chr2:179574308;179574307;179574306
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: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-81
• Domain position: 88
• Structural Position: 173
• Q(SASA): 0.2546
• 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/L	rs375212459	-0.13	0.379	None	0.587	0.428	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
S/L	rs375212459	-0.13	0.379	None	0.587	0.428	None	gnomAD-4.0.0	1.61279E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.05792E-05

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	0.1091	likely_benign	0.0973	benign	-0.866	Destabilizing	0.004	N	0.196	neutral	None	None	None	None	N
S/C	0.2989	likely_benign	0.2758	benign	-0.554	Destabilizing	0.977	D	0.56	neutral	None	None	None	None	N
S/D	0.8435	likely_pathogenic	0.7846	pathogenic	0.187	Stabilizing	0.005	N	0.306	neutral	None	None	None	None	N
S/E	0.8541	likely_pathogenic	0.8137	pathogenic	0.176	Stabilizing	0.447	N	0.51	neutral	None	None	None	None	N
S/F	0.4242	ambiguous	0.3786	ambiguous	-1.135	Destabilizing	0.92	D	0.64	neutral	None	None	None	None	N
S/G	0.2614	likely_benign	0.2173	benign	-1.08	Destabilizing	0.25	N	0.49	neutral	None	None	None	None	N
S/H	0.697	likely_pathogenic	0.6477	pathogenic	-1.518	Destabilizing	0.992	D	0.556	neutral	None	None	None	None	N
S/I	0.4679	ambiguous	0.4156	ambiguous	-0.403	Destabilizing	0.85	D	0.629	neutral	None	None	None	None	N
S/K	0.9423	likely_pathogenic	0.9162	pathogenic	-0.42	Destabilizing	0.617	D	0.51	neutral	None	None	None	None	N
S/L	0.1936	likely_benign	0.1649	benign	-0.403	Destabilizing	0.379	N	0.587	neutral	None	None	None	None	N
S/M	0.4029	ambiguous	0.3615	ambiguous	-0.142	Destabilizing	0.992	D	0.556	neutral	None	None	None	None	N
S/N	0.4025	ambiguous	0.3502	ambiguous	-0.316	Destabilizing	0.617	D	0.52	neutral	None	None	None	None	N
S/P	0.8372	likely_pathogenic	0.7694	pathogenic	-0.527	Destabilizing	0.896	D	0.575	neutral	None	None	None	None	N
S/Q	0.8001	likely_pathogenic	0.7637	pathogenic	-0.515	Destabilizing	0.92	D	0.54	neutral	None	None	None	None	N
S/R	0.8977	likely_pathogenic	0.8603	pathogenic	-0.37	Destabilizing	0.85	D	0.59	neutral	None	None	None	None	N
S/T	0.1457	likely_benign	0.134	benign	-0.453	Destabilizing	0.007	N	0.17	neutral	None	None	None	None	N
S/V	0.3738	ambiguous	0.3221	benign	-0.527	Destabilizing	0.447	N	0.601	neutral	None	None	None	None	N
S/W	0.6771	likely_pathogenic	0.6118	pathogenic	-1.027	Destabilizing	0.992	D	0.664	neutral	None	None	None	None	N
S/Y	0.388	ambiguous	0.3409	ambiguous	-0.772	Destabilizing	0.972	D	0.636	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.