TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1156	3691;3692;3693	chr2:178781178;178781177;178781176	chr2:179645905;179645904;179645903
N2AB	1156	3691;3692;3693	chr2:178781178;178781177;178781176	chr2:179645905;179645904;179645903
N2A	1156	3691;3692;3693	chr2:178781178;178781177;178781176	chr2:179645905;179645904;179645903
N2B	1110	3553;3554;3555	chr2:178781178;178781177;178781176	chr2:179645905;179645904;179645903
Novex-1	1110	3553;3554;3555	chr2:178781178;178781177;178781176	chr2:179645905;179645904;179645903
Novex-2	1110	3553;3554;3555	chr2:178781178;178781177;178781176	chr2:179645905;179645904;179645903
Novex-3	1156	3691;3692;3693	chr2:178781178;178781177;178781176	chr2:179645905;179645904;179645903

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-4
• Domain position: 75
• Structural Position: 156
• Q(SASA): 0.0607
• 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
I/T	None	None	0.722	N	0.74	0.339	0.537170616986	gnomAD-4.0.0	2.73646E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59733E-06	0	0
I/V	None	None	0.003	N	0.303	0.057	0.229924730088	gnomAD-4.0.0	1.59076E-06	None	None	None	None	N	None	0	0	None	4.76644E-05	0	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
I/A	0.7979	likely_pathogenic	0.7875	pathogenic	-2.545	Highly Destabilizing	0.415	N	0.725	prob.delet.	None	None	None	None	N
I/C	0.9579	likely_pathogenic	0.9526	pathogenic	-1.556	Destabilizing	0.024	N	0.637	neutral	None	None	None	None	N
I/D	0.9998	likely_pathogenic	0.9998	pathogenic	-3.279	Highly Destabilizing	0.987	D	0.853	deleterious	None	None	None	None	N
I/E	0.9991	likely_pathogenic	0.9991	pathogenic	-2.958	Highly Destabilizing	0.961	D	0.851	deleterious	None	None	None	None	N
I/F	0.8303	likely_pathogenic	0.836	pathogenic	-1.508	Destabilizing	0.901	D	0.702	prob.neutral	N	0.452093366	None	None	N
I/G	0.9938	likely_pathogenic	0.9939	pathogenic	-3.149	Highly Destabilizing	0.961	D	0.833	deleterious	None	None	None	None	N
I/H	0.9992	likely_pathogenic	0.9993	pathogenic	-2.903	Highly Destabilizing	0.996	D	0.864	deleterious	None	None	None	None	N
I/K	0.9987	likely_pathogenic	0.9988	pathogenic	-1.826	Destabilizing	0.961	D	0.852	deleterious	None	None	None	None	N
I/L	0.3746	ambiguous	0.376	ambiguous	-0.728	Destabilizing	0.19	N	0.421	neutral	N	0.430233725	None	None	N
I/M	0.3591	ambiguous	0.3539	ambiguous	-0.815	Destabilizing	0.901	D	0.673	neutral	N	0.455541523	None	None	N
I/N	0.996	likely_pathogenic	0.9965	pathogenic	-2.536	Highly Destabilizing	0.983	D	0.851	deleterious	N	0.456219242	None	None	N
I/P	0.9981	likely_pathogenic	0.9986	pathogenic	-1.324	Destabilizing	0.987	D	0.851	deleterious	None	None	None	None	N
I/Q	0.9982	likely_pathogenic	0.9982	pathogenic	-2.185	Highly Destabilizing	0.987	D	0.864	deleterious	None	None	None	None	N
I/R	0.9973	likely_pathogenic	0.9975	pathogenic	-1.935	Destabilizing	0.961	D	0.855	deleterious	None	None	None	None	N
I/S	0.9787	likely_pathogenic	0.9792	pathogenic	-3.065	Highly Destabilizing	0.901	D	0.797	deleterious	N	0.456486004	None	None	N
I/T	0.9234	likely_pathogenic	0.9195	pathogenic	-2.583	Highly Destabilizing	0.722	D	0.74	deleterious	N	0.454464237	None	None	N
I/V	0.082	likely_benign	0.0793	benign	-1.324	Destabilizing	0.003	N	0.303	neutral	N	0.392685548	None	None	N
I/W	0.9984	likely_pathogenic	0.9986	pathogenic	-1.957	Destabilizing	0.996	D	0.849	deleterious	None	None	None	None	N
I/Y	0.993	likely_pathogenic	0.9938	pathogenic	-1.697	Destabilizing	0.961	D	0.767	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.