TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35447	106564;106565;106566	chr2:178530276;178530275;178530274	chr2:179395003;179395002;179395001
N2AB	33806	101641;101642;101643	chr2:178530276;178530275;178530274	chr2:179395003;179395002;179395001
N2A	32879	98860;98861;98862	chr2:178530276;178530275;178530274	chr2:179395003;179395002;179395001
N2B	26382	79369;79370;79371	chr2:178530276;178530275;178530274	chr2:179395003;179395002;179395001
Novex-1	26507	79744;79745;79746	chr2:178530276;178530275;178530274	chr2:179395003;179395002;179395001
Novex-2	26574	79945;79946;79947	chr2:178530276;178530275;178530274	chr2:179395003;179395002;179395001
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-166
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.2006
• 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
P/R	None	None	0.986	D	0.571	0.627	0.565865824572	gnomAD-4.0.0	8.23794E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.08255E-05	0	0
P/S	None	None	0.271	D	0.254	0.552	0.379366414296	gnomAD-4.0.0	2.05894E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.70579E-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
P/A	0.4118	ambiguous	0.4231	ambiguous	-0.555	Destabilizing	0.664	D	0.436	neutral	D	0.545655813	None	None	I
P/C	0.9295	likely_pathogenic	0.9285	pathogenic	-0.601	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	I
P/D	0.8073	likely_pathogenic	0.8037	pathogenic	-0.452	Destabilizing	0.978	D	0.472	neutral	None	None	None	None	I
P/E	0.6715	likely_pathogenic	0.6545	pathogenic	-0.579	Destabilizing	0.927	D	0.463	neutral	None	None	None	None	I
P/F	0.8949	likely_pathogenic	0.8862	pathogenic	-0.843	Destabilizing	0.978	D	0.668	neutral	None	None	None	None	I
P/G	0.7357	likely_pathogenic	0.7257	pathogenic	-0.675	Destabilizing	0.927	D	0.508	neutral	None	None	None	None	I
P/H	0.7328	likely_pathogenic	0.7257	pathogenic	-0.284	Destabilizing	0.999	D	0.582	neutral	D	0.605277821	None	None	I
P/I	0.6543	likely_pathogenic	0.6492	pathogenic	-0.39	Destabilizing	0.957	D	0.633	neutral	None	None	None	None	I
P/K	0.7739	likely_pathogenic	0.7693	pathogenic	-0.506	Destabilizing	0.927	D	0.465	neutral	None	None	None	None	I
P/L	0.4595	ambiguous	0.4622	ambiguous	-0.39	Destabilizing	0.029	N	0.301	neutral	D	0.598545046	None	None	I
P/M	0.7215	likely_pathogenic	0.7194	pathogenic	-0.343	Destabilizing	0.978	D	0.584	neutral	None	None	None	None	I
P/N	0.7603	likely_pathogenic	0.7519	pathogenic	-0.209	Destabilizing	0.978	D	0.567	neutral	None	None	None	None	I
P/Q	0.6121	likely_pathogenic	0.5956	pathogenic	-0.493	Destabilizing	0.989	D	0.467	neutral	None	None	None	None	I
P/R	0.7041	likely_pathogenic	0.6973	pathogenic	0.056	Stabilizing	0.986	D	0.571	neutral	D	0.614160799	None	None	I
P/S	0.5986	likely_pathogenic	0.5916	pathogenic	-0.54	Destabilizing	0.271	N	0.254	neutral	D	0.535932122	None	None	I
P/T	0.4186	ambiguous	0.4201	ambiguous	-0.573	Destabilizing	0.905	D	0.442	neutral	D	0.604874213	None	None	I
P/V	0.5608	ambiguous	0.5568	ambiguous	-0.41	Destabilizing	0.864	D	0.517	neutral	None	None	None	None	I
P/W	0.953	likely_pathogenic	0.9479	pathogenic	-0.909	Destabilizing	0.999	D	0.694	prob.neutral	None	None	None	None	I
P/Y	0.87	likely_pathogenic	0.8617	pathogenic	-0.617	Destabilizing	0.996	D	0.671	neutral	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.