TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14488	43687;43688;43689	chr2:178632544;178632543;178632542	chr2:179497271;179497270;179497269
N2AB	12847	38764;38765;38766	chr2:178632544;178632543;178632542	chr2:179497271;179497270;179497269
N2A	11920	35983;35984;35985	chr2:178632544;178632543;178632542	chr2:179497271;179497270;179497269
N2B	5423	16492;16493;16494	chr2:178632544;178632543;178632542	chr2:179497271;179497270;179497269
Novex-1	5548	16867;16868;16869	chr2:178632544;178632543;178632542	chr2:179497271;179497270;179497269
Novex-2	5615	17068;17069;17070	chr2:178632544;178632543;178632542	chr2:179497271;179497270;179497269
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-95
• Domain position: 81
• Structural Position: 166
• Q(SASA): 0.1625
• 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
G/S	None	None	0.955	D	0.563	0.359	0.375861065471	gnomAD-4.0.0	6.84494E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.16125E-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
G/A	0.0922	likely_benign	0.0896	benign	-0.571	Destabilizing	0.053	N	0.369	neutral	N	0.329876385	None	None	N
G/C	0.4271	ambiguous	0.4268	ambiguous	-0.991	Destabilizing	0.999	D	0.807	deleterious	N	0.441698646	None	None	N
G/D	0.9519	likely_pathogenic	0.9548	pathogenic	-1.413	Destabilizing	0.997	D	0.727	prob.delet.	D	0.545191436	None	None	N
G/E	0.9385	likely_pathogenic	0.9428	pathogenic	-1.301	Destabilizing	0.995	D	0.713	prob.delet.	None	None	None	None	N
G/F	0.9772	likely_pathogenic	0.9748	pathogenic	-0.624	Destabilizing	0.998	D	0.81	deleterious	None	None	None	None	N
G/H	0.9676	likely_pathogenic	0.9643	pathogenic	-1.524	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
G/I	0.8892	likely_pathogenic	0.879	pathogenic	0.352	Stabilizing	0.995	D	0.788	deleterious	None	None	None	None	N
G/K	0.9717	likely_pathogenic	0.9711	pathogenic	-0.792	Destabilizing	0.995	D	0.722	prob.delet.	None	None	None	None	N
G/L	0.9004	likely_pathogenic	0.8894	pathogenic	0.352	Stabilizing	0.99	D	0.736	prob.delet.	None	None	None	None	N
G/M	0.9324	likely_pathogenic	0.9256	pathogenic	0.019	Stabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
G/N	0.9313	likely_pathogenic	0.9295	pathogenic	-0.881	Destabilizing	0.998	D	0.727	prob.delet.	None	None	None	None	N
G/P	0.9947	likely_pathogenic	0.9933	pathogenic	0.089	Stabilizing	0.998	D	0.761	deleterious	None	None	None	None	N
G/Q	0.9267	likely_pathogenic	0.9234	pathogenic	-0.795	Destabilizing	0.998	D	0.782	deleterious	None	None	None	None	N
G/R	0.8859	likely_pathogenic	0.8862	pathogenic	-0.916	Destabilizing	0.997	D	0.761	deleterious	D	0.544442258	None	None	N
G/S	0.1815	likely_benign	0.1824	benign	-1.281	Destabilizing	0.955	D	0.563	neutral	D	0.529156576	None	None	N
G/T	0.5474	ambiguous	0.5273	ambiguous	-1.05	Destabilizing	0.995	D	0.705	prob.neutral	None	None	None	None	N
G/V	0.6863	likely_pathogenic	0.6729	pathogenic	0.089	Stabilizing	0.987	D	0.73	prob.delet.	D	0.529722195	None	None	N
G/W	0.9631	likely_pathogenic	0.9603	pathogenic	-1.279	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
G/Y	0.9662	likely_pathogenic	0.9645	pathogenic	-0.683	Destabilizing	1.0	D	0.806	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.