TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26546	79861;79862;79863	chr2:178566496;178566495;178566494	chr2:179431223;179431222;179431221
N2AB	24905	74938;74939;74940	chr2:178566496;178566495;178566494	chr2:179431223;179431222;179431221
N2A	23978	72157;72158;72159	chr2:178566496;178566495;178566494	chr2:179431223;179431222;179431221
N2B	17481	52666;52667;52668	chr2:178566496;178566495;178566494	chr2:179431223;179431222;179431221
Novex-1	17606	53041;53042;53043	chr2:178566496;178566495;178566494	chr2:179431223;179431222;179431221
Novex-2	17673	53242;53243;53244	chr2:178566496;178566495;178566494	chr2:179431223;179431222;179431221
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-81
• Domain position: 60
• Structural Position: 89
• Q(SASA): 0.1388
• 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
T/A	rs775053902	-0.491	0.928	N	0.522	0.322	0.181679512989	gnomAD-2.1.1	2.42E-05	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	4.45E-05	0
T/A	rs775053902	-0.491	0.928	N	0.522	0.322	0.181679512989	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
T/A	rs775053902	-0.491	0.928	N	0.522	0.322	0.181679512989	gnomAD-4.0.0	5.45432E-05	None	None	None	None	N	None	0	5.00267E-05	None	0	0	None	0	0	7.12058E-05	0	1.60154E-05

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
T/A	0.1049	likely_benign	0.0975	benign	-0.723	Destabilizing	0.928	D	0.522	neutral	N	0.499692666	None	None	N
T/C	0.27	likely_benign	0.2669	benign	-0.418	Destabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	N
T/D	0.4782	ambiguous	0.4451	ambiguous	-0.28	Destabilizing	0.968	D	0.621	neutral	None	None	None	None	N
T/E	0.468	ambiguous	0.4291	ambiguous	-0.154	Destabilizing	0.983	D	0.619	neutral	None	None	None	None	N
T/F	0.4194	ambiguous	0.3936	ambiguous	-0.768	Destabilizing	0.997	D	0.753	deleterious	None	None	None	None	N
T/G	0.2133	likely_benign	0.2189	benign	-1.049	Destabilizing	0.895	D	0.607	neutral	None	None	None	None	N
T/H	0.2882	likely_benign	0.2666	benign	-1.053	Destabilizing	0.996	D	0.759	deleterious	None	None	None	None	N
T/I	0.3874	ambiguous	0.3651	ambiguous	0.092	Stabilizing	0.989	D	0.668	neutral	N	0.506440616	None	None	N
T/K	0.2584	likely_benign	0.229	benign	-0.129	Destabilizing	0.968	D	0.625	neutral	None	None	None	None	N
T/L	0.1148	likely_benign	0.1101	benign	0.092	Stabilizing	0.972	D	0.581	neutral	None	None	None	None	N
T/M	0.1073	likely_benign	0.1021	benign	-0.072	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	N
T/N	0.0861	likely_benign	0.0775	benign	-0.6	Destabilizing	0.085	N	0.405	neutral	N	0.469218148	None	None	N
T/P	0.1032	likely_benign	0.1034	benign	-0.149	Destabilizing	0.989	D	0.669	neutral	N	0.471459873	None	None	N
T/Q	0.2314	likely_benign	0.2109	benign	-0.471	Destabilizing	0.983	D	0.695	prob.neutral	None	None	None	None	N
T/R	0.2289	likely_benign	0.1968	benign	-0.149	Destabilizing	0.983	D	0.667	neutral	None	None	None	None	N
T/S	0.1104	likely_benign	0.1088	benign	-0.901	Destabilizing	0.865	D	0.536	neutral	N	0.505426658	None	None	N
T/V	0.2587	likely_benign	0.2438	benign	-0.149	Destabilizing	0.972	D	0.551	neutral	None	None	None	None	N
T/W	0.7397	likely_pathogenic	0.716	pathogenic	-0.882	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
T/Y	0.3871	ambiguous	0.3563	ambiguous	-0.48	Destabilizing	0.997	D	0.755	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.