TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13897	41914;41915;41916	chr2:178635635;178635634;178635633	chr2:179500362;179500361;179500360
N2AB	12256	36991;36992;36993	chr2:178635635;178635634;178635633	chr2:179500362;179500361;179500360
N2A	11329	34210;34211;34212	chr2:178635635;178635634;178635633	chr2:179500362;179500361;179500360
N2B	4832	14719;14720;14721	chr2:178635635;178635634;178635633	chr2:179500362;179500361;179500360
Novex-1	4957	15094;15095;15096	chr2:178635635;178635634;178635633	chr2:179500362;179500361;179500360
Novex-2	5024	15295;15296;15297	chr2:178635635;178635634;178635633	chr2:179500362;179500361;179500360
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-89
• Domain position: 22
• Structural Position: 35
• Q(SASA): 0.1278
• 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	rs1288360484	None	0.058	N	0.611	0.24	0.537125817887	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/T	rs1288360484	None	0.058	N	0.611	0.24	0.537125817887	gnomAD-4.0.0	3.75826E-06	None	None	None	None	N	None	1.33837E-05	0	None	0	0	None	0	0	4.27117E-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	0.7474	likely_pathogenic	0.8082	pathogenic	-2.293	Highly Destabilizing	0.016	N	0.545	neutral	None	None	None	None	N
I/C	0.9437	likely_pathogenic	0.9544	pathogenic	-1.518	Destabilizing	0.685	D	0.609	neutral	None	None	None	None	N
I/D	0.995	likely_pathogenic	0.9972	pathogenic	-1.971	Destabilizing	0.637	D	0.772	deleterious	None	None	None	None	N
I/E	0.9865	likely_pathogenic	0.9915	pathogenic	-1.896	Destabilizing	0.366	N	0.752	deleterious	None	None	None	None	N
I/F	0.4259	ambiguous	0.4938	ambiguous	-1.548	Destabilizing	0.125	N	0.615	neutral	None	None	None	None	N
I/G	0.9792	likely_pathogenic	0.9869	pathogenic	-2.719	Highly Destabilizing	0.366	N	0.735	deleterious	None	None	None	None	N
I/H	0.9761	likely_pathogenic	0.9863	pathogenic	-1.94	Destabilizing	0.869	D	0.725	deleterious	None	None	None	None	N
I/K	0.9554	likely_pathogenic	0.9753	pathogenic	-1.698	Destabilizing	0.303	N	0.741	deleterious	N	0.47597012	None	None	N
I/L	0.1526	likely_benign	0.1779	benign	-1.135	Destabilizing	None	N	0.156	neutral	N	0.416910772	None	None	N
I/M	0.222	likely_benign	0.2302	benign	-0.872	Destabilizing	0.097	N	0.621	neutral	N	0.450021927	None	None	N
I/N	0.9565	likely_pathogenic	0.9716	pathogenic	-1.606	Destabilizing	0.637	D	0.767	deleterious	None	None	None	None	N
I/P	0.9826	likely_pathogenic	0.9888	pathogenic	-1.494	Destabilizing	0.637	D	0.772	deleterious	None	None	None	None	N
I/Q	0.9735	likely_pathogenic	0.9834	pathogenic	-1.711	Destabilizing	0.637	D	0.747	deleterious	None	None	None	None	N
I/R	0.9338	likely_pathogenic	0.9631	pathogenic	-1.118	Destabilizing	0.303	N	0.771	deleterious	N	0.47597012	None	None	N
I/S	0.9081	likely_pathogenic	0.9337	pathogenic	-2.301	Highly Destabilizing	0.075	N	0.682	prob.neutral	None	None	None	None	N
I/T	0.5418	ambiguous	0.6432	pathogenic	-2.095	Highly Destabilizing	0.058	N	0.611	neutral	N	0.472846359	None	None	N
I/V	0.106	likely_benign	0.1097	benign	-1.494	Destabilizing	None	N	0.173	neutral	N	0.439690125	None	None	N
I/W	0.966	likely_pathogenic	0.9804	pathogenic	-1.699	Destabilizing	0.869	D	0.741	deleterious	None	None	None	None	N
I/Y	0.9061	likely_pathogenic	0.9358	pathogenic	-1.498	Destabilizing	0.366	N	0.693	prob.delet.	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.