TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7003	21232;21233;21234	chr2:178724368;178724367;178724366	chr2:179589095;179589094;179589093
N2AB	6686	20281;20282;20283	chr2:178724368;178724367;178724366	chr2:179589095;179589094;179589093
N2A	5759	17500;17501;17502	chr2:178724368;178724367;178724366	chr2:179589095;179589094;179589093
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: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-54
• Domain position: 56
• Structural Position: 136
• Q(SASA): 0.055
• 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/A	None	None	0.02	N	0.433	0.092	0.0666544352282	gnomAD-4.0.0	1.36862E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79915E-06	0	0
S/P	None	None	0.991	N	0.782	0.255	0.173771789658	gnomAD-4.0.0	6.84311E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99577E-07	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
S/A	0.0659	likely_benign	0.0684	benign	-0.62	Destabilizing	0.02	N	0.433	neutral	N	0.378998484	None	None	N
S/C	0.148	likely_benign	0.1365	benign	-0.049	Destabilizing	0.999	D	0.763	deleterious	N	0.44349268	None	None	N
S/D	0.983	likely_pathogenic	0.9774	pathogenic	-0.938	Destabilizing	0.993	D	0.686	prob.neutral	None	None	None	None	N
S/E	0.9873	likely_pathogenic	0.9831	pathogenic	-0.686	Destabilizing	0.953	D	0.686	prob.neutral	None	None	None	None	N
S/F	0.7417	likely_pathogenic	0.6615	pathogenic	-0.566	Destabilizing	0.997	D	0.8	deleterious	N	0.470561851	None	None	N
S/G	0.2282	likely_benign	0.1914	benign	-1.046	Destabilizing	0.807	D	0.679	prob.neutral	None	None	None	None	N
S/H	0.9285	likely_pathogenic	0.8944	pathogenic	-1.258	Destabilizing	0.999	D	0.766	deleterious	None	None	None	None	N
S/I	0.6354	likely_pathogenic	0.5876	pathogenic	0.492	Stabilizing	0.986	D	0.795	deleterious	None	None	None	None	N
S/K	0.9967	likely_pathogenic	0.9949	pathogenic	0.749	Stabilizing	0.953	D	0.674	neutral	None	None	None	None	N
S/L	0.3774	ambiguous	0.3324	benign	0.492	Stabilizing	0.953	D	0.761	deleterious	None	None	None	None	N
S/M	0.6386	likely_pathogenic	0.5985	pathogenic	0.281	Stabilizing	0.999	D	0.769	deleterious	None	None	None	None	N
S/N	0.8514	likely_pathogenic	0.7877	pathogenic	-0.117	Destabilizing	0.993	D	0.713	prob.delet.	None	None	None	None	N
S/P	0.9458	likely_pathogenic	0.9316	pathogenic	0.154	Stabilizing	0.991	D	0.782	deleterious	N	0.472122076	None	None	N
S/Q	0.9681	likely_pathogenic	0.9569	pathogenic	0.228	Stabilizing	0.993	D	0.754	deleterious	None	None	None	None	N
S/R	0.991	likely_pathogenic	0.9859	pathogenic	0.097	Stabilizing	0.993	D	0.795	deleterious	None	None	None	None	N
S/T	0.2237	likely_benign	0.2135	benign	0.208	Stabilizing	0.939	D	0.67	neutral	N	0.45449632	None	None	N
S/V	0.4855	ambiguous	0.462	ambiguous	0.154	Stabilizing	0.91	D	0.753	deleterious	None	None	None	None	N
S/W	0.9089	likely_pathogenic	0.8642	pathogenic	-0.805	Destabilizing	0.999	D	0.782	deleterious	None	None	None	None	N
S/Y	0.7433	likely_pathogenic	0.654	pathogenic	-0.292	Destabilizing	0.997	D	0.795	deleterious	N	0.456093831	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.