TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30597	92014;92015;92016	chr2:178550049;178550048;178550047	chr2:179414776;179414775;179414774
N2AB	28956	87091;87092;87093	chr2:178550049;178550048;178550047	chr2:179414776;179414775;179414774
N2A	28029	84310;84311;84312	chr2:178550049;178550048;178550047	chr2:179414776;179414775;179414774
N2B	21532	64819;64820;64821	chr2:178550049;178550048;178550047	chr2:179414776;179414775;179414774
Novex-1	21657	65194;65195;65196	chr2:178550049;178550048;178550047	chr2:179414776;179414775;179414774
Novex-2	21724	65395;65396;65397	chr2:178550049;178550048;178550047	chr2:179414776;179414775;179414774
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-149
• Domain position: 66
• Structural Position: 154
• Q(SASA): 0.1037
• 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
Y/H	None	None	1.0	D	0.795	0.831	0.763337080039	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	1.01626E-03	None	0	0	None	0	0	0	0	3.66327E-05
Y/N	None	None	1.0	D	0.876	0.834	0.933793615972	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
Y/A	0.9955	likely_pathogenic	0.996	pathogenic	-2.161	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
Y/C	0.8708	likely_pathogenic	0.889	pathogenic	-1.685	Destabilizing	1.0	D	0.833	deleterious	D	0.658763183	None	None	N
Y/D	0.9976	likely_pathogenic	0.9978	pathogenic	-2.71	Highly Destabilizing	1.0	D	0.881	deleterious	D	0.658763183	None	None	N
Y/E	0.9989	likely_pathogenic	0.9989	pathogenic	-2.456	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
Y/F	0.1013	likely_benign	0.1065	benign	-0.692	Destabilizing	0.999	D	0.706	prob.neutral	D	0.601055984	None	None	N
Y/G	0.9935	likely_pathogenic	0.9937	pathogenic	-2.624	Highly Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
Y/H	0.9572	likely_pathogenic	0.9562	pathogenic	-1.998	Destabilizing	1.0	D	0.795	deleterious	D	0.658561378	None	None	N
Y/I	0.8927	likely_pathogenic	0.9059	pathogenic	-0.636	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
Y/K	0.9988	likely_pathogenic	0.9987	pathogenic	-1.87	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
Y/L	0.8131	likely_pathogenic	0.8386	pathogenic	-0.636	Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	N
Y/M	0.9511	likely_pathogenic	0.9541	pathogenic	-0.785	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
Y/N	0.9861	likely_pathogenic	0.9865	pathogenic	-2.795	Highly Destabilizing	1.0	D	0.876	deleterious	D	0.658763183	None	None	N
Y/P	0.9986	likely_pathogenic	0.9986	pathogenic	-1.159	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
Y/Q	0.9978	likely_pathogenic	0.9978	pathogenic	-2.31	Highly Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
Y/R	0.9951	likely_pathogenic	0.9949	pathogenic	-2.179	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
Y/S	0.9888	likely_pathogenic	0.9893	pathogenic	-3.138	Highly Destabilizing	1.0	D	0.881	deleterious	D	0.658763183	None	None	N
Y/T	0.9944	likely_pathogenic	0.9951	pathogenic	-2.732	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
Y/V	0.8862	likely_pathogenic	0.9029	pathogenic	-1.159	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
Y/W	0.6914	likely_pathogenic	0.6983	pathogenic	-0.086	Destabilizing	1.0	D	0.781	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.