TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21743	65452;65453;65454	chr2:178584324;178584323;178584322	chr2:179449051;179449050;179449049
N2AB	20102	60529;60530;60531	chr2:178584324;178584323;178584322	chr2:179449051;179449050;179449049
N2A	19175	57748;57749;57750	chr2:178584324;178584323;178584322	chr2:179449051;179449050;179449049
N2B	12678	38257;38258;38259	chr2:178584324;178584323;178584322	chr2:179449051;179449050;179449049
Novex-1	12803	38632;38633;38634	chr2:178584324;178584323;178584322	chr2:179449051;179449050;179449049
Novex-2	12870	38833;38834;38835	chr2:178584324;178584323;178584322	chr2:179449051;179449050;179449049
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Fn3-45
• Domain position: 85
• Structural Position: 118
• Q(SASA): 0.0721
• 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/T	None	None	0.98	N	0.742	0.345	0.309530620856	gnomAD-4.0.0	6.89624E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.06193E-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	0.5739	likely_pathogenic	0.5468	ambiguous	-0.983	Destabilizing	0.871	D	0.586	neutral	None	None	None	None	N
S/C	0.8023	likely_pathogenic	0.7891	pathogenic	-0.752	Destabilizing	1.0	D	0.768	deleterious	N	0.518176812	None	None	N
S/D	0.9959	likely_pathogenic	0.9949	pathogenic	-1.04	Destabilizing	0.985	D	0.748	deleterious	None	None	None	None	N
S/E	0.9984	likely_pathogenic	0.9982	pathogenic	-0.926	Destabilizing	0.995	D	0.76	deleterious	None	None	None	None	N
S/F	0.9961	likely_pathogenic	0.995	pathogenic	-0.773	Destabilizing	0.999	D	0.78	deleterious	None	None	None	None	N
S/G	0.1746	likely_benign	0.1537	benign	-1.316	Destabilizing	0.011	N	0.459	neutral	N	0.402702063	None	None	N
S/H	0.9919	likely_pathogenic	0.9889	pathogenic	-1.558	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
S/I	0.9963	likely_pathogenic	0.9958	pathogenic	-0.162	Destabilizing	0.998	D	0.805	deleterious	N	0.506567018	None	None	N
S/K	0.9993	likely_pathogenic	0.9992	pathogenic	-0.649	Destabilizing	0.985	D	0.765	deleterious	None	None	None	None	N
S/L	0.9771	likely_pathogenic	0.9717	pathogenic	-0.162	Destabilizing	0.985	D	0.803	deleterious	None	None	None	None	N
S/M	0.9917	likely_pathogenic	0.9899	pathogenic	-0.157	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
S/N	0.9789	likely_pathogenic	0.9782	pathogenic	-0.959	Destabilizing	0.98	D	0.741	deleterious	N	0.517162854	None	None	N
S/P	0.9953	likely_pathogenic	0.994	pathogenic	-0.402	Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
S/Q	0.9963	likely_pathogenic	0.9955	pathogenic	-0.929	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
S/R	0.9987	likely_pathogenic	0.9984	pathogenic	-0.729	Destabilizing	0.998	D	0.797	deleterious	N	0.499312089	None	None	N
S/T	0.8589	likely_pathogenic	0.8473	pathogenic	-0.818	Destabilizing	0.98	D	0.742	deleterious	N	0.504792591	None	None	N
S/V	0.9934	likely_pathogenic	0.9922	pathogenic	-0.402	Destabilizing	0.999	D	0.794	deleterious	None	None	None	None	N
S/W	0.9983	likely_pathogenic	0.9975	pathogenic	-0.854	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
S/Y	0.995	likely_pathogenic	0.9936	pathogenic	-0.525	Destabilizing	0.999	D	0.781	deleterious	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.