TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24254	72985;72986;72987	chr2:178573372;178573371;178573370	chr2:179438099;179438098;179438097
N2AB	22613	68062;68063;68064	chr2:178573372;178573371;178573370	chr2:179438099;179438098;179438097
N2A	21686	65281;65282;65283	chr2:178573372;178573371;178573370	chr2:179438099;179438098;179438097
N2B	15189	45790;45791;45792	chr2:178573372;178573371;178573370	chr2:179438099;179438098;179438097
Novex-1	15314	46165;46166;46167	chr2:178573372;178573371;178573370	chr2:179438099;179438098;179438097
Novex-2	15381	46366;46367;46368	chr2:178573372;178573371;178573370	chr2:179438099;179438098;179438097
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: Fn3-64
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.1574
• 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
I/N	None	None	0.999	D	0.839	0.542	0.896069202243	gnomAD-4.0.0	1.85578E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	2.69687E-04	0	0	0
I/V	None	None	0.889	N	0.472	0.171	0.50055108712	gnomAD-4.0.0	1.85602E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.25837E-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	0.9739	likely_pathogenic	0.9663	pathogenic	-2.56	Highly Destabilizing	0.996	D	0.682	prob.neutral	None	None	None	None	I
I/C	0.9802	likely_pathogenic	0.9756	pathogenic	-1.756	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
I/D	0.997	likely_pathogenic	0.9956	pathogenic	-2.627	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
I/E	0.9932	likely_pathogenic	0.9906	pathogenic	-2.492	Highly Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	I
I/F	0.9045	likely_pathogenic	0.8651	pathogenic	-1.647	Destabilizing	0.997	D	0.729	prob.delet.	D	0.53836189	None	None	I
I/G	0.994	likely_pathogenic	0.9912	pathogenic	-3.032	Highly Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
I/H	0.9946	likely_pathogenic	0.9914	pathogenic	-2.303	Highly Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
I/K	0.9818	likely_pathogenic	0.9727	pathogenic	-1.924	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
I/L	0.4915	ambiguous	0.4295	ambiguous	-1.234	Destabilizing	0.104	N	0.304	neutral	N	0.501646401	None	None	I
I/M	0.5161	ambiguous	0.442	ambiguous	-1.02	Destabilizing	0.997	D	0.724	prob.delet.	D	0.545669725	None	None	I
I/N	0.9461	likely_pathogenic	0.922	pathogenic	-2.017	Highly Destabilizing	0.999	D	0.839	deleterious	D	0.553267049	None	None	I
I/P	0.97	likely_pathogenic	0.9603	pathogenic	-1.653	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	I
I/Q	0.9913	likely_pathogenic	0.9865	pathogenic	-2.049	Highly Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	I
I/R	0.9804	likely_pathogenic	0.9689	pathogenic	-1.396	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
I/S	0.9798	likely_pathogenic	0.9716	pathogenic	-2.712	Highly Destabilizing	0.999	D	0.791	deleterious	D	0.55250658	None	None	I
I/T	0.9614	likely_pathogenic	0.949	pathogenic	-2.448	Highly Destabilizing	0.998	D	0.808	deleterious	D	0.537529424	None	None	I
I/V	0.1546	likely_benign	0.1503	benign	-1.653	Destabilizing	0.889	D	0.472	neutral	N	0.508518098	None	None	I
I/W	0.9961	likely_pathogenic	0.9942	pathogenic	-1.927	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
I/Y	0.9803	likely_pathogenic	0.9709	pathogenic	-1.7	Destabilizing	1.0	D	0.797	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.