TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25789	77590;77591;77592	chr2:178568767;178568766;178568765	chr2:179433494;179433493;179433492
N2AB	24148	72667;72668;72669	chr2:178568767;178568766;178568765	chr2:179433494;179433493;179433492
N2A	23221	69886;69887;69888	chr2:178568767;178568766;178568765	chr2:179433494;179433493;179433492
N2B	16724	50395;50396;50397	chr2:178568767;178568766;178568765	chr2:179433494;179433493;179433492
Novex-1	16849	50770;50771;50772	chr2:178568767;178568766;178568765	chr2:179433494;179433493;179433492
Novex-2	16916	50971;50972;50973	chr2:178568767;178568766;178568765	chr2:179433494;179433493;179433492
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: Fn3-75
• Domain position: 92
• Structural Position: 127
• Q(SASA): 0.179
• 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/L	rs1253687329	None	None	N	0.219	0.052	0.315314060047	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
I/V	rs1253687329	None	None	N	0.155	0.05	0.314417295294	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.5625	ambiguous	0.4603	ambiguous	-2.278	Highly Destabilizing	0.016	N	0.569	neutral	None	None	None	None	N
I/C	0.8853	likely_pathogenic	0.845	pathogenic	-1.497	Destabilizing	0.366	N	0.608	neutral	None	None	None	None	N
I/D	0.9896	likely_pathogenic	0.9848	pathogenic	-2.869	Highly Destabilizing	0.366	N	0.681	prob.neutral	None	None	None	None	N
I/E	0.9655	likely_pathogenic	0.9512	pathogenic	-2.622	Highly Destabilizing	0.366	N	0.692	prob.delet.	None	None	None	None	N
I/F	0.5252	ambiguous	0.4222	ambiguous	-1.404	Destabilizing	0.075	N	0.635	neutral	None	None	None	None	N
I/G	0.952	likely_pathogenic	0.927	pathogenic	-2.792	Highly Destabilizing	0.141	N	0.691	prob.delet.	None	None	None	None	N
I/H	0.9549	likely_pathogenic	0.9306	pathogenic	-2.167	Highly Destabilizing	0.869	D	0.67	prob.neutral	None	None	None	None	N
I/K	0.9333	likely_pathogenic	0.9001	pathogenic	-1.918	Destabilizing	0.11	N	0.695	prob.delet.	N	0.473300433	None	None	N
I/L	0.2297	likely_benign	0.1776	benign	-0.781	Destabilizing	None	N	0.219	neutral	N	0.488750541	None	None	N
I/M	0.2135	likely_benign	0.17	benign	-0.676	Destabilizing	0.177	N	0.595	neutral	N	0.474060902	None	None	N
I/N	0.915	likely_pathogenic	0.8811	pathogenic	-2.427	Highly Destabilizing	0.637	D	0.659	prob.neutral	None	None	None	None	N
I/P	0.9777	likely_pathogenic	0.9716	pathogenic	-1.264	Destabilizing	0.366	N	0.675	prob.neutral	None	None	None	None	N
I/Q	0.9388	likely_pathogenic	0.9093	pathogenic	-2.253	Highly Destabilizing	0.637	D	0.647	neutral	None	None	None	None	N
I/R	0.9017	likely_pathogenic	0.8563	pathogenic	-1.699	Destabilizing	0.303	N	0.664	prob.neutral	N	0.471526007	None	None	N
I/S	0.7908	likely_pathogenic	0.7183	pathogenic	-3.012	Highly Destabilizing	0.075	N	0.621	neutral	None	None	None	None	N
I/T	0.408	ambiguous	0.3152	benign	-2.615	Highly Destabilizing	0.012	N	0.637	neutral	N	0.458141785	None	None	N
I/V	0.057	likely_benign	0.0536	benign	-1.264	Destabilizing	None	N	0.155	neutral	N	0.368635136	None	None	N
I/W	0.9766	likely_pathogenic	0.9664	pathogenic	-1.77	Destabilizing	0.869	D	0.689	prob.delet.	None	None	None	None	N
I/Y	0.9139	likely_pathogenic	0.8783	pathogenic	-1.436	Destabilizing	0.366	N	0.679	prob.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.