TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24039	72340;72341;72342	chr2:178574017;178574016;178574015	chr2:179438744;179438743;179438742
N2AB	22398	67417;67418;67419	chr2:178574017;178574016;178574015	chr2:179438744;179438743;179438742
N2A	21471	64636;64637;64638	chr2:178574017;178574016;178574015	chr2:179438744;179438743;179438742
N2B	14974	45145;45146;45147	chr2:178574017;178574016;178574015	chr2:179438744;179438743;179438742
Novex-1	15099	45520;45521;45522	chr2:178574017;178574016;178574015	chr2:179438744;179438743;179438742
Novex-2	15166	45721;45722;45723	chr2:178574017;178574016;178574015	chr2:179438744;179438743;179438742
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-131
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.2349
• Predicted PPI site: I

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/G	None	None	0.667	D	0.525	0.546	0.884044859232	gnomAD-4.0.0	2.05312E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69877E-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
V/A	0.2741	likely_benign	0.3374	benign	-1.652	Destabilizing	0.104	N	0.429	neutral	N	0.493586957	None	None	I
V/C	0.7403	likely_pathogenic	0.7907	pathogenic	-1.247	Destabilizing	0.968	D	0.495	neutral	None	None	None	None	I
V/D	0.6028	likely_pathogenic	0.6681	pathogenic	-1.486	Destabilizing	0.667	D	0.58	neutral	D	0.537610281	None	None	I
V/E	0.4518	ambiguous	0.518	ambiguous	-1.313	Destabilizing	0.726	D	0.51	neutral	None	None	None	None	I
V/F	0.1672	likely_benign	0.2072	benign	-0.96	Destabilizing	0.331	N	0.478	neutral	N	0.516023306	None	None	I
V/G	0.4259	ambiguous	0.4888	ambiguous	-2.14	Highly Destabilizing	0.667	D	0.525	neutral	D	0.536849813	None	None	I
V/H	0.6253	likely_pathogenic	0.693	pathogenic	-1.695	Destabilizing	0.968	D	0.585	neutral	None	None	None	None	I
V/I	0.067	likely_benign	0.0687	benign	-0.332	Destabilizing	None	N	0.127	neutral	N	0.470051003	None	None	I
V/K	0.4628	ambiguous	0.5113	ambiguous	-1.316	Destabilizing	0.726	D	0.505	neutral	None	None	None	None	I
V/L	0.1111	likely_benign	0.1255	benign	-0.332	Destabilizing	None	N	0.129	neutral	N	0.503104783	None	None	I
V/M	0.1154	likely_benign	0.1392	benign	-0.413	Destabilizing	0.567	D	0.489	neutral	None	None	None	None	I
V/N	0.4331	ambiguous	0.5063	ambiguous	-1.478	Destabilizing	0.89	D	0.588	neutral	None	None	None	None	I
V/P	0.8296	likely_pathogenic	0.8604	pathogenic	-0.741	Destabilizing	0.89	D	0.539	neutral	None	None	None	None	I
V/Q	0.4396	ambiguous	0.5021	ambiguous	-1.357	Destabilizing	0.89	D	0.551	neutral	None	None	None	None	I
V/R	0.431	ambiguous	0.4757	ambiguous	-1.151	Destabilizing	0.726	D	0.587	neutral	None	None	None	None	I
V/S	0.3873	ambiguous	0.4615	ambiguous	-2.159	Highly Destabilizing	0.726	D	0.457	neutral	None	None	None	None	I
V/T	0.2827	likely_benign	0.345	ambiguous	-1.829	Destabilizing	0.272	N	0.417	neutral	None	None	None	None	I
V/W	0.778	likely_pathogenic	0.8377	pathogenic	-1.306	Destabilizing	0.968	D	0.625	neutral	None	None	None	None	I
V/Y	0.509	ambiguous	0.5799	pathogenic	-0.921	Destabilizing	0.726	D	0.519	neutral	None	None	None	None	I

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.