TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21556	64891;64892;64893	chr2:178585078;178585077;178585076	chr2:179449805;179449804;179449803
N2AB	19915	59968;59969;59970	chr2:178585078;178585077;178585076	chr2:179449805;179449804;179449803
N2A	18988	57187;57188;57189	chr2:178585078;178585077;178585076	chr2:179449805;179449804;179449803
N2B	12491	37696;37697;37698	chr2:178585078;178585077;178585076	chr2:179449805;179449804;179449803
Novex-1	12616	38071;38072;38073	chr2:178585078;178585077;178585076	chr2:179449805;179449804;179449803
Novex-2	12683	38272;38273;38274	chr2:178585078;178585077;178585076	chr2:179449805;179449804;179449803
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-124
• Domain position: 88
• Structural Position: 177
• Q(SASA): 0.435
• 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	None	None	0.978	D	0.605	0.682	0.83087589604	gnomAD-4.0.0	1.37696E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80586E-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	0.9107	likely_pathogenic	0.8949	pathogenic	-1.664	Destabilizing	0.978	D	0.605	neutral	D	0.608070926	None	None	N
V/C	0.9792	likely_pathogenic	0.9746	pathogenic	-1.232	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
V/D	0.9985	likely_pathogenic	0.9982	pathogenic	-1.573	Destabilizing	0.999	D	0.7	prob.neutral	D	0.592656978	None	None	N
V/E	0.9958	likely_pathogenic	0.9951	pathogenic	-1.554	Destabilizing	0.999	D	0.668	neutral	None	None	None	None	N
V/F	0.9688	likely_pathogenic	0.9663	pathogenic	-1.302	Destabilizing	0.997	D	0.685	prob.neutral	D	0.592051565	None	None	N
V/G	0.973	likely_pathogenic	0.9666	pathogenic	-2.001	Highly Destabilizing	0.999	D	0.677	prob.neutral	D	0.608676339	None	None	N
V/H	0.9989	likely_pathogenic	0.9987	pathogenic	-1.52	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	N
V/I	0.1243	likely_benign	0.1174	benign	-0.82	Destabilizing	0.37	N	0.477	neutral	N	0.514791575	None	None	N
V/K	0.9971	likely_pathogenic	0.9964	pathogenic	-1.262	Destabilizing	0.999	D	0.667	neutral	None	None	None	None	N
V/L	0.9138	likely_pathogenic	0.907	pathogenic	-0.82	Destabilizing	0.9	D	0.628	neutral	D	0.580514771	None	None	N
V/M	0.9193	likely_pathogenic	0.9058	pathogenic	-0.683	Destabilizing	0.998	D	0.719	prob.delet.	None	None	None	None	N
V/N	0.9918	likely_pathogenic	0.9888	pathogenic	-1.105	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
V/P	0.9801	likely_pathogenic	0.9812	pathogenic	-1.068	Destabilizing	0.999	D	0.676	prob.neutral	None	None	None	None	N
V/Q	0.996	likely_pathogenic	0.995	pathogenic	-1.278	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	N
V/R	0.9947	likely_pathogenic	0.9937	pathogenic	-0.792	Destabilizing	0.999	D	0.704	prob.neutral	None	None	None	None	N
V/S	0.9653	likely_pathogenic	0.956	pathogenic	-1.679	Destabilizing	0.999	D	0.642	neutral	None	None	None	None	N
V/T	0.8456	likely_pathogenic	0.8036	pathogenic	-1.55	Destabilizing	0.992	D	0.68	prob.neutral	None	None	None	None	N
V/W	0.9996	likely_pathogenic	0.9996	pathogenic	-1.489	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	N
V/Y	0.9977	likely_pathogenic	0.9975	pathogenic	-1.193	Destabilizing	0.999	D	0.69	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.