TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14603	44032;44033;44034	chr2:178631241;178631240;178631239	chr2:179495968;179495967;179495966
N2AB	12962	39109;39110;39111	chr2:178631241;178631240;178631239	chr2:179495968;179495967;179495966
N2A	12035	36328;36329;36330	chr2:178631241;178631240;178631239	chr2:179495968;179495967;179495966
N2B	5538	16837;16838;16839	chr2:178631241;178631240;178631239	chr2:179495968;179495967;179495966
Novex-1	5663	17212;17213;17214	chr2:178631241;178631240;178631239	chr2:179495968;179495967;179495966
Novex-2	5730	17413;17414;17415	chr2:178631241;178631240;178631239	chr2:179495968;179495967;179495966
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-97
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.1411
• 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
V/I	rs2154220273	None	0.987	N	0.515	0.2	0.356072328145	gnomAD-4.0.0	3.18894E-06	None	None	None	None	N	None	0	0	None	0	5.58005E-05	None	0	0	0	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
V/A	0.5804	likely_pathogenic	0.5185	ambiguous	-1.653	Destabilizing	0.543	D	0.294	neutral	N	0.458003572	None	None	N
V/C	0.9516	likely_pathogenic	0.9337	pathogenic	-1.305	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
V/D	0.9594	likely_pathogenic	0.9645	pathogenic	-1.466	Destabilizing	0.998	D	0.805	deleterious	D	0.673291774	None	None	N
V/E	0.9366	likely_pathogenic	0.9305	pathogenic	-1.276	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
V/F	0.5438	ambiguous	0.5075	ambiguous	-0.9	Destabilizing	0.999	D	0.795	deleterious	D	0.559785526	None	None	N
V/G	0.716	likely_pathogenic	0.7047	pathogenic	-2.17	Highly Destabilizing	0.997	D	0.736	prob.delet.	D	0.602853936	None	None	N
V/H	0.9836	likely_pathogenic	0.9816	pathogenic	-1.73	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
V/I	0.104	likely_benign	0.1037	benign	-0.249	Destabilizing	0.987	D	0.515	neutral	N	0.462879045	None	None	N
V/K	0.9508	likely_pathogenic	0.9519	pathogenic	-1.289	Destabilizing	0.999	D	0.77	deleterious	None	None	None	None	N
V/L	0.5472	ambiguous	0.5064	ambiguous	-0.249	Destabilizing	0.973	D	0.53	neutral	N	0.457662966	None	None	N
V/M	0.4322	ambiguous	0.3723	ambiguous	-0.367	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
V/N	0.9127	likely_pathogenic	0.9162	pathogenic	-1.508	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
V/P	0.9896	likely_pathogenic	0.9912	pathogenic	-0.685	Destabilizing	0.999	D	0.796	deleterious	None	None	None	None	N
V/Q	0.9523	likely_pathogenic	0.9423	pathogenic	-1.363	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
V/R	0.9406	likely_pathogenic	0.9376	pathogenic	-1.142	Destabilizing	0.999	D	0.812	deleterious	None	None	None	None	N
V/S	0.8568	likely_pathogenic	0.8396	pathogenic	-2.237	Highly Destabilizing	0.995	D	0.735	prob.delet.	None	None	None	None	N
V/T	0.6971	likely_pathogenic	0.6583	pathogenic	-1.888	Destabilizing	0.992	D	0.576	neutral	None	None	None	None	N
V/W	0.9854	likely_pathogenic	0.9829	pathogenic	-1.276	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
V/Y	0.9236	likely_pathogenic	0.9148	pathogenic	-0.877	Destabilizing	1.0	D	0.803	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.