TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22850	68773;68774;68775	chr2:178577878;178577877;178577876	chr2:179442605;179442604;179442603
N2AB	21209	63850;63851;63852	chr2:178577878;178577877;178577876	chr2:179442605;179442604;179442603
N2A	20282	61069;61070;61071	chr2:178577878;178577877;178577876	chr2:179442605;179442604;179442603
N2B	13785	41578;41579;41580	chr2:178577878;178577877;178577876	chr2:179442605;179442604;179442603
Novex-1	13910	41953;41954;41955	chr2:178577878;178577877;178577876	chr2:179442605;179442604;179442603
Novex-2	13977	42154;42155;42156	chr2:178577878;178577877;178577876	chr2:179442605;179442604;179442603
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-54
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.3399
• 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
V/F	rs934106303	None	0.994	N	0.741	0.4	0.733297738924	gnomAD-4.0.0	1.6628E-06	None	None	None	None	N	None	6.06281E-05	0	None	0	0	None	0	0	0	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
V/A	0.2909	likely_benign	0.3337	benign	-1.47	Destabilizing	0.892	D	0.517	neutral	N	0.472517226	None	None	N
V/C	0.8438	likely_pathogenic	0.8557	pathogenic	-1.087	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
V/D	0.8444	likely_pathogenic	0.8493	pathogenic	-1.382	Destabilizing	0.025	N	0.477	neutral	N	0.509675025	None	None	N
V/E	0.7989	likely_pathogenic	0.8112	pathogenic	-1.304	Destabilizing	0.845	D	0.654	neutral	None	None	None	None	N
V/F	0.4262	ambiguous	0.4573	ambiguous	-0.946	Destabilizing	0.994	D	0.741	deleterious	N	0.510619169	None	None	N
V/G	0.5003	ambiguous	0.5223	ambiguous	-1.857	Destabilizing	0.967	D	0.724	prob.delet.	N	0.520017372	None	None	N
V/H	0.9259	likely_pathogenic	0.9333	pathogenic	-1.307	Destabilizing	0.999	D	0.768	deleterious	None	None	None	None	N
V/I	0.0881	likely_benign	0.0884	benign	-0.481	Destabilizing	0.873	D	0.561	neutral	N	0.492297852	None	None	N
V/K	0.8373	likely_pathogenic	0.8552	pathogenic	-1.315	Destabilizing	0.975	D	0.726	prob.delet.	None	None	None	None	N
V/L	0.4159	ambiguous	0.443	ambiguous	-0.481	Destabilizing	0.873	D	0.524	neutral	N	0.517521583	None	None	N
V/M	0.3133	likely_benign	0.3203	benign	-0.484	Destabilizing	0.996	D	0.635	neutral	None	None	None	None	N
V/N	0.7004	likely_pathogenic	0.7151	pathogenic	-1.314	Destabilizing	0.95	D	0.775	deleterious	None	None	None	None	N
V/P	0.4334	ambiguous	0.4753	ambiguous	-0.777	Destabilizing	0.987	D	0.759	deleterious	None	None	None	None	N
V/Q	0.8406	likely_pathogenic	0.8516	pathogenic	-1.351	Destabilizing	0.987	D	0.765	deleterious	None	None	None	None	N
V/R	0.8098	likely_pathogenic	0.8366	pathogenic	-0.9	Destabilizing	0.987	D	0.79	deleterious	None	None	None	None	N
V/S	0.5977	likely_pathogenic	0.6291	pathogenic	-1.872	Destabilizing	0.975	D	0.685	prob.neutral	None	None	None	None	N
V/T	0.4866	ambiguous	0.5218	ambiguous	-1.662	Destabilizing	0.916	D	0.589	neutral	None	None	None	None	N
V/W	0.9538	likely_pathogenic	0.9569	pathogenic	-1.217	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
V/Y	0.7972	likely_pathogenic	0.8183	pathogenic	-0.875	Destabilizing	0.996	D	0.736	prob.delet.	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.