TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25809	77650;77651;77652	chr2:178568707;178568706;178568705	chr2:179433434;179433433;179433432
N2AB	24168	72727;72728;72729	chr2:178568707;178568706;178568705	chr2:179433434;179433433;179433432
N2A	23241	69946;69947;69948	chr2:178568707;178568706;178568705	chr2:179433434;179433433;179433432
N2B	16744	50455;50456;50457	chr2:178568707;178568706;178568705	chr2:179433434;179433433;179433432
Novex-1	16869	50830;50831;50832	chr2:178568707;178568706;178568705	chr2:179433434;179433433;179433432
Novex-2	16936	51031;51032;51033	chr2:178568707;178568706;178568705	chr2:179433434;179433433;179433432
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-136
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.2626
• 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/A	rs367819941	-1.555	0.645	N	0.428	0.405	None	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
V/A	rs367819941	-1.555	0.645	N	0.428	0.405	None	gnomAD-4.0.0	1.59225E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4334E-05	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	0.3725	ambiguous	0.4104	ambiguous	-1.19	Destabilizing	0.645	D	0.428	neutral	N	0.48772438	None	None	N
V/C	0.7757	likely_pathogenic	0.7656	pathogenic	-0.901	Destabilizing	0.995	D	0.635	neutral	None	None	None	None	N
V/D	0.9396	likely_pathogenic	0.9522	pathogenic	-0.759	Destabilizing	0.945	D	0.707	prob.neutral	None	None	None	None	N
V/E	0.8621	likely_pathogenic	0.8839	pathogenic	-0.819	Destabilizing	0.928	D	0.643	neutral	D	0.53123118	None	None	N
V/F	0.4791	ambiguous	0.4859	ambiguous	-1.144	Destabilizing	0.894	D	0.654	neutral	None	None	None	None	N
V/G	0.5953	likely_pathogenic	0.6656	pathogenic	-1.433	Destabilizing	0.928	D	0.691	prob.neutral	D	0.527356839	None	None	N
V/H	0.9283	likely_pathogenic	0.9394	pathogenic	-0.985	Destabilizing	0.995	D	0.689	prob.neutral	None	None	None	None	N
V/I	0.0859	likely_benign	0.0745	benign	-0.656	Destabilizing	0.006	N	0.236	neutral	N	0.488484849	None	None	N
V/K	0.8377	likely_pathogenic	0.8629	pathogenic	-0.886	Destabilizing	0.945	D	0.643	neutral	None	None	None	None	N
V/L	0.3433	ambiguous	0.3119	benign	-0.656	Destabilizing	0.114	N	0.389	neutral	N	0.492968301	None	None	N
V/M	0.2856	likely_benign	0.2747	benign	-0.489	Destabilizing	0.894	D	0.697	prob.neutral	None	None	None	None	N
V/N	0.8131	likely_pathogenic	0.8337	pathogenic	-0.589	Destabilizing	0.981	D	0.716	prob.delet.	None	None	None	None	N
V/P	0.9706	likely_pathogenic	0.973	pathogenic	-0.799	Destabilizing	0.981	D	0.667	neutral	None	None	None	None	N
V/Q	0.7787	likely_pathogenic	0.8153	pathogenic	-0.833	Destabilizing	0.981	D	0.672	neutral	None	None	None	None	N
V/R	0.7892	likely_pathogenic	0.8244	pathogenic	-0.37	Destabilizing	0.945	D	0.717	prob.delet.	None	None	None	None	N
V/S	0.5805	likely_pathogenic	0.6294	pathogenic	-1.102	Destabilizing	0.945	D	0.654	neutral	None	None	None	None	N
V/T	0.3887	ambiguous	0.4514	ambiguous	-1.055	Destabilizing	0.707	D	0.63	neutral	None	None	None	None	N
V/W	0.9755	likely_pathogenic	0.9757	pathogenic	-1.228	Destabilizing	0.995	D	0.669	neutral	None	None	None	None	N
V/Y	0.892	likely_pathogenic	0.8965	pathogenic	-0.939	Destabilizing	0.945	D	0.66	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.