TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22393	67402;67403;67404	chr2:178580110;178580109;178580108	chr2:179444837;179444836;179444835
N2AB	20752	62479;62480;62481	chr2:178580110;178580109;178580108	chr2:179444837;179444836;179444835
N2A	19825	59698;59699;59700	chr2:178580110;178580109;178580108	chr2:179444837;179444836;179444835
N2B	13328	40207;40208;40209	chr2:178580110;178580109;178580108	chr2:179444837;179444836;179444835
Novex-1	13453	40582;40583;40584	chr2:178580110;178580109;178580108	chr2:179444837;179444836;179444835
Novex-2	13520	40783;40784;40785	chr2:178580110;178580109;178580108	chr2:179444837;179444836;179444835
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-50
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.2728
• 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
K/R	None	None	0.999	N	0.74	0.369	0.388812400583	gnomAD-4.0.0	1.59213E-06	None	None	None	None	N	None	0	0	None	0	2.77516E-05	None	0	0	0	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
K/A	0.9666	likely_pathogenic	0.9502	pathogenic	-1.481	Destabilizing	0.999	D	0.764	deleterious	None	None	None	None	N
K/C	0.9223	likely_pathogenic	0.8561	pathogenic	-1.377	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
K/D	0.9967	likely_pathogenic	0.9966	pathogenic	-1.958	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
K/E	0.9253	likely_pathogenic	0.8978	pathogenic	-1.619	Destabilizing	0.999	D	0.753	deleterious	N	0.516478065	None	None	N
K/F	0.9775	likely_pathogenic	0.952	pathogenic	-0.768	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
K/G	0.9823	likely_pathogenic	0.9737	pathogenic	-1.983	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
K/H	0.8229	likely_pathogenic	0.7674	pathogenic	-1.713	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
K/I	0.847	likely_pathogenic	0.7549	pathogenic	-0.035	Destabilizing	1.0	D	0.885	deleterious	N	0.4703416	None	None	N
K/L	0.8299	likely_pathogenic	0.7232	pathogenic	-0.035	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
K/M	0.6895	likely_pathogenic	0.5346	ambiguous	-0.432	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
K/N	0.9842	likely_pathogenic	0.9796	pathogenic	-1.729	Destabilizing	1.0	D	0.855	deleterious	D	0.527998954	None	None	N
K/P	0.9991	likely_pathogenic	0.9991	pathogenic	-0.5	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
K/Q	0.5988	likely_pathogenic	0.5099	ambiguous	-1.298	Destabilizing	1.0	D	0.857	deleterious	N	0.497057136	None	None	N
K/R	0.1532	likely_benign	0.1457	benign	-0.676	Destabilizing	0.999	D	0.74	deleterious	N	0.507840521	None	None	N
K/S	0.9799	likely_pathogenic	0.9698	pathogenic	-2.268	Highly Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
K/T	0.8933	likely_pathogenic	0.8396	pathogenic	-1.65	Destabilizing	1.0	D	0.827	deleterious	N	0.493485511	None	None	N
K/V	0.819	likely_pathogenic	0.7292	pathogenic	-0.5	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
K/W	0.973	likely_pathogenic	0.948	pathogenic	-0.794	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
K/Y	0.921	likely_pathogenic	0.8553	pathogenic	-0.444	Destabilizing	1.0	D	0.869	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.