TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21554	64885;64886;64887	chr2:178585084;178585083;178585082	chr2:179449811;179449810;179449809
N2AB	19913	59962;59963;59964	chr2:178585084;178585083;178585082	chr2:179449811;179449810;179449809
N2A	18986	57181;57182;57183	chr2:178585084;178585083;178585082	chr2:179449811;179449810;179449809
N2B	12489	37690;37691;37692	chr2:178585084;178585083;178585082	chr2:179449811;179449810;179449809
Novex-1	12614	38065;38066;38067	chr2:178585084;178585083;178585082	chr2:179449811;179449810;179449809
Novex-2	12681	38266;38267;38268	chr2:178585084;178585083;178585082	chr2:179449811;179449810;179449809
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-124
• Domain position: 86
• Structural Position: 174
• Q(SASA): 0.1636
• 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/G	None	None	0.781	N	0.854	0.481	0.750149104527	gnomAD-4.0.0	3.22615E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.93617E-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	0.7916	likely_pathogenic	0.8364	pathogenic	-2.101	Highly Destabilizing	0.334	N	0.572	neutral	N	0.504683097	None	None	N
V/C	0.9536	likely_pathogenic	0.9582	pathogenic	-1.484	Destabilizing	0.982	D	0.797	deleterious	None	None	None	None	N
V/D	0.996	likely_pathogenic	0.9974	pathogenic	-2.921	Highly Destabilizing	0.781	D	0.86	deleterious	N	0.505190076	None	None	N
V/E	0.9907	likely_pathogenic	0.9936	pathogenic	-2.614	Highly Destabilizing	0.826	D	0.847	deleterious	None	None	None	None	N
V/F	0.6761	likely_pathogenic	0.697	pathogenic	-1.196	Destabilizing	0.638	D	0.819	deleterious	N	0.503922628	None	None	N
V/G	0.9235	likely_pathogenic	0.9428	pathogenic	-2.715	Highly Destabilizing	0.781	D	0.854	deleterious	N	0.49383377	None	None	N
V/H	0.9962	likely_pathogenic	0.9974	pathogenic	-2.655	Highly Destabilizing	0.982	D	0.84	deleterious	None	None	None	None	N
V/I	0.0812	likely_benign	0.0787	benign	-0.331	Destabilizing	0.002	N	0.213	neutral	N	0.465004102	None	None	N
V/K	0.9939	likely_pathogenic	0.9957	pathogenic	-1.687	Destabilizing	0.826	D	0.848	deleterious	None	None	None	None	N
V/L	0.4054	ambiguous	0.4401	ambiguous	-0.331	Destabilizing	0.034	N	0.555	neutral	N	0.426082276	None	None	N
V/M	0.4696	ambiguous	0.5155	ambiguous	-0.476	Destabilizing	0.7	D	0.746	deleterious	None	None	None	None	N
V/N	0.9881	likely_pathogenic	0.9913	pathogenic	-2.304	Highly Destabilizing	0.935	D	0.868	deleterious	None	None	None	None	N
V/P	0.9887	likely_pathogenic	0.9928	pathogenic	-0.899	Destabilizing	0.935	D	0.839	deleterious	None	None	None	None	N
V/Q	0.9917	likely_pathogenic	0.9942	pathogenic	-1.96	Destabilizing	0.935	D	0.853	deleterious	None	None	None	None	N
V/R	0.9906	likely_pathogenic	0.9932	pathogenic	-1.79	Destabilizing	0.826	D	0.865	deleterious	None	None	None	None	N
V/S	0.9669	likely_pathogenic	0.976	pathogenic	-2.867	Highly Destabilizing	0.826	D	0.84	deleterious	None	None	None	None	N
V/T	0.8554	likely_pathogenic	0.885	pathogenic	-2.395	Highly Destabilizing	0.399	N	0.677	prob.neutral	None	None	None	None	N
V/W	0.9927	likely_pathogenic	0.9944	pathogenic	-1.808	Destabilizing	0.982	D	0.829	deleterious	None	None	None	None	N
V/Y	0.9711	likely_pathogenic	0.9761	pathogenic	-1.402	Destabilizing	0.826	D	0.807	deleterious	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.