TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34975	105148;105149;105150	chr2:178531692;178531691;178531690	chr2:179396419;179396418;179396417
N2AB	33334	100225;100226;100227	chr2:178531692;178531691;178531690	chr2:179396419;179396418;179396417
N2A	32407	97444;97445;97446	chr2:178531692;178531691;178531690	chr2:179396419;179396418;179396417
N2B	25910	77953;77954;77955	chr2:178531692;178531691;178531690	chr2:179396419;179396418;179396417
Novex-1	26035	78328;78329;78330	chr2:178531692;178531691;178531690	chr2:179396419;179396418;179396417
Novex-2	26102	78529;78530;78531	chr2:178531692;178531691;178531690	chr2:179396419;179396418;179396417
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Ig-163
• Domain position: 34
• Structural Position: 48
• Q(SASA): 0.1277
• 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
W/L	None	None	0.885	D	0.797	0.869	0.947801904728	gnomAD-4.0.0	6.84141E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.994E-07	0	0
W/R	None	None	0.997	D	0.862	0.925	0.932282890813	gnomAD-4.0.0	1.59089E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85757E-06	0	0
W/S	rs1181086213	None	0.982	D	0.86	0.914	0.959178105942	gnomAD-4.0.0	1.36828E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.7988E-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
W/A	0.9938	likely_pathogenic	0.9966	pathogenic	-2.744	Highly Destabilizing	0.91	D	0.821	deleterious	None	None	None	None	N
W/C	0.9955	likely_pathogenic	0.9981	pathogenic	-1.469	Destabilizing	0.1	N	0.743	deleterious	D	0.68449228	None	None	N
W/D	0.9995	likely_pathogenic	0.9997	pathogenic	-3.468	Highly Destabilizing	0.998	D	0.856	deleterious	None	None	None	None	N
W/E	0.9996	likely_pathogenic	0.9998	pathogenic	-3.344	Highly Destabilizing	0.998	D	0.865	deleterious	None	None	None	None	N
W/F	0.5843	likely_pathogenic	0.7235	pathogenic	-1.847	Destabilizing	0.998	D	0.791	deleterious	None	None	None	None	N
W/G	0.9785	likely_pathogenic	0.9856	pathogenic	-2.985	Highly Destabilizing	0.991	D	0.809	deleterious	D	0.684290476	None	None	N
W/H	0.9982	likely_pathogenic	0.999	pathogenic	-2.434	Highly Destabilizing	0.999	D	0.82	deleterious	None	None	None	None	N
W/I	0.9596	likely_pathogenic	0.9807	pathogenic	-1.827	Destabilizing	0.986	D	0.867	deleterious	None	None	None	None	N
W/K	0.9998	likely_pathogenic	0.9999	pathogenic	-2.583	Highly Destabilizing	0.998	D	0.862	deleterious	None	None	None	None	N
W/L	0.9173	likely_pathogenic	0.9526	pathogenic	-1.827	Destabilizing	0.885	D	0.797	deleterious	D	0.636000228	None	None	N
W/M	0.9835	likely_pathogenic	0.9919	pathogenic	-1.31	Destabilizing	0.999	D	0.778	deleterious	None	None	None	None	N
W/N	0.9992	likely_pathogenic	0.9996	pathogenic	-3.372	Highly Destabilizing	0.998	D	0.862	deleterious	None	None	None	None	N
W/P	0.9992	likely_pathogenic	0.9995	pathogenic	-2.162	Highly Destabilizing	0.998	D	0.86	deleterious	None	None	None	None	N
W/Q	0.9998	likely_pathogenic	0.9999	pathogenic	-3.103	Highly Destabilizing	0.998	D	0.848	deleterious	None	None	None	None	N
W/R	0.9995	likely_pathogenic	0.9998	pathogenic	-2.602	Highly Destabilizing	0.997	D	0.862	deleterious	D	0.68449228	None	None	N
W/S	0.9959	likely_pathogenic	0.9977	pathogenic	-3.383	Highly Destabilizing	0.982	D	0.86	deleterious	D	0.68449228	None	None	N
W/T	0.9953	likely_pathogenic	0.9976	pathogenic	-3.178	Highly Destabilizing	0.986	D	0.815	deleterious	None	None	None	None	N
W/V	0.9684	likely_pathogenic	0.9851	pathogenic	-2.162	Highly Destabilizing	0.986	D	0.855	deleterious	None	None	None	None	N
W/Y	0.8988	likely_pathogenic	0.9392	pathogenic	-1.74	Destabilizing	0.998	D	0.801	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.