TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14040	42343;42344;42345	chr2:178634756;178634755;178634754	chr2:179499483;179499482;179499481
N2AB	12399	37420;37421;37422	chr2:178634756;178634755;178634754	chr2:179499483;179499482;179499481
N2A	11472	34639;34640;34641	chr2:178634756;178634755;178634754	chr2:179499483;179499482;179499481
N2B	4975	15148;15149;15150	chr2:178634756;178634755;178634754	chr2:179499483;179499482;179499481
Novex-1	5100	15523;15524;15525	chr2:178634756;178634755;178634754	chr2:179499483;179499482;179499481
Novex-2	5167	15724;15725;15726	chr2:178634756;178634755;178634754	chr2:179499483;179499482;179499481
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-90
• Domain position: 76
• Structural Position: 161
• Q(SASA): 0.7834
• 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
N/Y	rs2154228320	None	1.0	D	0.723	0.584	0.578910049572	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	2.07211E-04	0
N/Y	rs2154228320	None	1.0	D	0.723	0.584	0.578910049572	gnomAD-4.0.0	6.57056E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.07383E-04	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
N/A	0.9081	likely_pathogenic	0.869	pathogenic	-0.149	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	I
N/C	0.9122	likely_pathogenic	0.9157	pathogenic	0.264	Stabilizing	1.0	D	0.752	deleterious	None	None	None	None	I
N/D	0.4023	ambiguous	0.3565	ambiguous	0.22	Stabilizing	0.997	D	0.696	prob.delet.	N	0.454019298	None	None	I
N/E	0.9263	likely_pathogenic	0.8961	pathogenic	0.178	Stabilizing	0.998	D	0.744	deleterious	None	None	None	None	I
N/F	0.9821	likely_pathogenic	0.9787	pathogenic	-0.624	Destabilizing	1.0	D	0.733	deleterious	None	None	None	None	I
N/G	0.6015	likely_pathogenic	0.5363	ambiguous	-0.292	Destabilizing	0.998	D	0.617	neutral	None	None	None	None	I
N/H	0.5291	ambiguous	0.5064	ambiguous	-0.292	Destabilizing	0.999	D	0.769	deleterious	D	0.561382528	None	None	I
N/I	0.9809	likely_pathogenic	0.9745	pathogenic	0.133	Stabilizing	0.999	D	0.751	deleterious	D	0.563200792	None	None	I
N/K	0.9512	likely_pathogenic	0.921	pathogenic	0.143	Stabilizing	0.999	D	0.747	deleterious	N	0.448982031	None	None	I
N/L	0.9381	likely_pathogenic	0.9228	pathogenic	0.133	Stabilizing	0.999	D	0.678	prob.neutral	None	None	None	None	I
N/M	0.9644	likely_pathogenic	0.9569	pathogenic	0.225	Stabilizing	1.0	D	0.732	deleterious	None	None	None	None	I
N/P	0.9567	likely_pathogenic	0.9489	pathogenic	0.065	Stabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	I
N/Q	0.9177	likely_pathogenic	0.8861	pathogenic	-0.24	Destabilizing	0.999	D	0.71	prob.delet.	None	None	None	None	I
N/R	0.9457	likely_pathogenic	0.9166	pathogenic	0.183	Stabilizing	0.999	D	0.721	deleterious	None	None	None	None	I
N/S	0.2997	likely_benign	0.2637	benign	-0.044	Destabilizing	0.997	D	0.627	neutral	N	0.514339533	None	None	I
N/T	0.7058	likely_pathogenic	0.6418	pathogenic	0.047	Stabilizing	0.997	D	0.738	deleterious	N	0.493852362	None	None	I
N/V	0.9713	likely_pathogenic	0.9613	pathogenic	0.065	Stabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	I
N/W	0.9914	likely_pathogenic	0.9916	pathogenic	-0.699	Destabilizing	1.0	D	0.704	prob.delet.	None	None	None	None	I
N/Y	0.8415	likely_pathogenic	0.8167	pathogenic	-0.388	Destabilizing	1.0	D	0.723	deleterious	D	0.562138348	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.