TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15738	47437;47438;47439	chr2:178618246;178618245;178618244	chr2:179482973;179482972;179482971
N2AB	14097	42514;42515;42516	chr2:178618246;178618245;178618244	chr2:179482973;179482972;179482971
N2A	13170	39733;39734;39735	chr2:178618246;178618245;178618244	chr2:179482973;179482972;179482971
N2B	6673	20242;20243;20244	chr2:178618246;178618245;178618244	chr2:179482973;179482972;179482971
Novex-1	6798	20617;20618;20619	chr2:178618246;178618245;178618244	chr2:179482973;179482972;179482971
Novex-2	6865	20818;20819;20820	chr2:178618246;178618245;178618244	chr2:179482973;179482972;179482971
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: Fn3-1
• Domain position: 82
• Structural Position: 114
• Q(SASA): 0.4941
• 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/A	None	None	0.999	N	0.548	0.369	0.457286136841	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
V/A	0.4298	ambiguous	0.4529	ambiguous	-0.533	Destabilizing	0.999	D	0.548	neutral	N	0.475800158	None	None	I
V/C	0.8857	likely_pathogenic	0.8273	pathogenic	-0.82	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	I
V/D	0.9479	likely_pathogenic	0.9355	pathogenic	-0.389	Destabilizing	1.0	D	0.825	deleterious	D	0.565605931	None	None	I
V/E	0.8758	likely_pathogenic	0.8373	pathogenic	-0.505	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	I
V/F	0.4608	ambiguous	0.3579	ambiguous	-0.729	Destabilizing	1.0	D	0.769	deleterious	N	0.484382644	None	None	I
V/G	0.6781	likely_pathogenic	0.6758	pathogenic	-0.644	Destabilizing	1.0	D	0.785	deleterious	N	0.507852798	None	None	I
V/H	0.9364	likely_pathogenic	0.887	pathogenic	-0.077	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
V/I	0.1479	likely_benign	0.1498	benign	-0.39	Destabilizing	0.997	D	0.462	neutral	N	0.482780367	None	None	I
V/K	0.9046	likely_pathogenic	0.849	pathogenic	-0.512	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
V/L	0.6988	likely_pathogenic	0.6785	pathogenic	-0.39	Destabilizing	0.997	D	0.541	neutral	N	0.482500658	None	None	I
V/M	0.5647	likely_pathogenic	0.5385	ambiguous	-0.482	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
V/N	0.8559	likely_pathogenic	0.7936	pathogenic	-0.351	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
V/P	0.9744	likely_pathogenic	0.9711	pathogenic	-0.404	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
V/Q	0.8542	likely_pathogenic	0.7864	pathogenic	-0.604	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
V/R	0.8298	likely_pathogenic	0.7393	pathogenic	0.067	Stabilizing	1.0	D	0.842	deleterious	None	None	None	None	I
V/S	0.665	likely_pathogenic	0.6335	pathogenic	-0.707	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
V/T	0.5623	ambiguous	0.5576	ambiguous	-0.724	Destabilizing	0.999	D	0.696	prob.neutral	None	None	None	None	I
V/W	0.9664	likely_pathogenic	0.9522	pathogenic	-0.768	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	I
V/Y	0.8778	likely_pathogenic	0.7884	pathogenic	-0.497	Destabilizing	1.0	D	0.771	deleterious	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.