TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16817	50674;50675;50676	chr2:178611860;178611859;178611858	chr2:179476587;179476586;179476585
N2AB	15176	45751;45752;45753	chr2:178611860;178611859;178611858	chr2:179476587;179476586;179476585
N2A	14249	42970;42971;42972	chr2:178611860;178611859;178611858	chr2:179476587;179476586;179476585
N2B	7752	23479;23480;23481	chr2:178611860;178611859;178611858	chr2:179476587;179476586;179476585
Novex-1	7877	23854;23855;23856	chr2:178611860;178611859;178611858	chr2:179476587;179476586;179476585
Novex-2	7944	24055;24056;24057	chr2:178611860;178611859;178611858	chr2:179476587;179476586;179476585
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-10
• Domain position: 67
• Structural Position: 98
• Q(SASA): 0.5422
• 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
I/F	rs2056387870	None	1.0	N	0.641	0.253	0.448597761117	gnomAD-4.0.0	3.18618E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72298E-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
I/A	0.5014	ambiguous	0.5179	ambiguous	-0.628	Destabilizing	0.999	D	0.457	neutral	None	None	None	None	N
I/C	0.929	likely_pathogenic	0.903	pathogenic	-0.733	Destabilizing	1.0	D	0.623	neutral	None	None	None	None	N
I/D	0.8301	likely_pathogenic	0.8542	pathogenic	-0.046	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	N
I/E	0.7255	likely_pathogenic	0.7564	pathogenic	-0.121	Destabilizing	1.0	D	0.662	neutral	None	None	None	None	N
I/F	0.3616	ambiguous	0.3736	ambiguous	-0.541	Destabilizing	1.0	D	0.641	neutral	N	0.481901133	None	None	N
I/G	0.8581	likely_pathogenic	0.8664	pathogenic	-0.803	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
I/H	0.815	likely_pathogenic	0.7996	pathogenic	-0.016	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	N
I/K	0.7025	likely_pathogenic	0.6907	pathogenic	-0.347	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	N
I/L	0.1933	likely_benign	0.1947	benign	-0.284	Destabilizing	0.993	D	0.261	neutral	N	0.475029052	None	None	N
I/M	0.169	likely_benign	0.1623	benign	-0.441	Destabilizing	1.0	D	0.629	neutral	N	0.478467527	None	None	N
I/N	0.5645	likely_pathogenic	0.582	pathogenic	-0.229	Destabilizing	1.0	D	0.678	prob.neutral	N	0.468562094	None	None	N
I/P	0.8935	likely_pathogenic	0.8899	pathogenic	-0.366	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
I/Q	0.6801	likely_pathogenic	0.6753	pathogenic	-0.414	Destabilizing	1.0	D	0.656	neutral	None	None	None	None	N
I/R	0.5997	likely_pathogenic	0.5918	pathogenic	0.182	Stabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
I/S	0.5069	ambiguous	0.5251	ambiguous	-0.715	Destabilizing	1.0	D	0.632	neutral	N	0.458501586	None	None	N
I/T	0.3179	likely_benign	0.3177	benign	-0.676	Destabilizing	1.0	D	0.577	neutral	N	0.463065737	None	None	N
I/V	0.1487	likely_benign	0.1533	benign	-0.366	Destabilizing	0.993	D	0.258	neutral	N	0.469766204	None	None	N
I/W	0.9011	likely_pathogenic	0.882	pathogenic	-0.555	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
I/Y	0.7946	likely_pathogenic	0.7756	pathogenic	-0.31	Destabilizing	1.0	D	0.652	neutral	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.