TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22916	68971;68972;68973	chr2:178577680;178577679;178577678	chr2:179442407;179442406;179442405
N2AB	21275	64048;64049;64050	chr2:178577680;178577679;178577678	chr2:179442407;179442406;179442405
N2A	20348	61267;61268;61269	chr2:178577680;178577679;178577678	chr2:179442407;179442406;179442405
N2B	13851	41776;41777;41778	chr2:178577680;178577679;178577678	chr2:179442407;179442406;179442405
Novex-1	13976	42151;42152;42153	chr2:178577680;178577679;178577678	chr2:179442407;179442406;179442405
Novex-2	14043	42352;42353;42354	chr2:178577680;178577679;178577678	chr2:179442407;179442406;179442405
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-54
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.0553
• 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	0.201	N	0.634	0.587	0.606545613963	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-06	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	0.8733	likely_pathogenic	0.8878	pathogenic	-3.148	Highly Destabilizing	0.25	N	0.622	neutral	None	None	None	None	N
I/C	0.8847	likely_pathogenic	0.905	pathogenic	-2.321	Highly Destabilizing	0.947	D	0.691	prob.neutral	None	None	None	None	N
I/D	0.9986	likely_pathogenic	0.9989	pathogenic	-3.626	Highly Destabilizing	0.826	D	0.851	deleterious	None	None	None	None	N
I/E	0.9967	likely_pathogenic	0.9968	pathogenic	-3.322	Highly Destabilizing	0.826	D	0.84	deleterious	None	None	None	None	N
I/F	0.8446	likely_pathogenic	0.8632	pathogenic	-1.735	Destabilizing	0.638	D	0.606	neutral	N	0.517535384	None	None	N
I/G	0.9869	likely_pathogenic	0.9884	pathogenic	-3.713	Highly Destabilizing	0.826	D	0.833	deleterious	None	None	None	None	N
I/H	0.9971	likely_pathogenic	0.9975	pathogenic	-3.19	Highly Destabilizing	0.982	D	0.845	deleterious	None	None	None	None	N
I/K	0.9954	likely_pathogenic	0.9956	pathogenic	-2.291	Highly Destabilizing	0.826	D	0.842	deleterious	None	None	None	None	N
I/L	0.4028	ambiguous	0.3931	ambiguous	-1.434	Destabilizing	0.043	N	0.317	neutral	N	0.514057204	None	None	N
I/M	0.5021	ambiguous	0.5154	ambiguous	-1.707	Destabilizing	0.638	D	0.612	neutral	N	0.479769938	None	None	N
I/N	0.9783	likely_pathogenic	0.9798	pathogenic	-2.92	Highly Destabilizing	0.916	D	0.863	deleterious	N	0.518295852	None	None	N
I/P	0.9941	likely_pathogenic	0.9947	pathogenic	-1.999	Destabilizing	0.935	D	0.865	deleterious	None	None	None	None	N
I/Q	0.9945	likely_pathogenic	0.9949	pathogenic	-2.607	Highly Destabilizing	0.935	D	0.869	deleterious	None	None	None	None	N
I/R	0.9918	likely_pathogenic	0.9924	pathogenic	-2.214	Highly Destabilizing	0.826	D	0.865	deleterious	None	None	None	None	N
I/S	0.946	likely_pathogenic	0.9502	pathogenic	-3.473	Highly Destabilizing	0.638	D	0.754	deleterious	N	0.506774963	None	None	N
I/T	0.92	likely_pathogenic	0.9235	pathogenic	-3.024	Highly Destabilizing	0.201	N	0.634	neutral	N	0.506521473	None	None	N
I/V	0.0922	likely_benign	0.0874	benign	-1.999	Destabilizing	0.001	N	0.188	neutral	N	0.329236093	None	None	N
I/W	0.998	likely_pathogenic	0.9985	pathogenic	-2.086	Highly Destabilizing	0.982	D	0.813	deleterious	None	None	None	None	N
I/Y	0.9865	likely_pathogenic	0.9889	pathogenic	-2.0	Highly Destabilizing	0.826	D	0.674	neutral	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.