TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14116	42571;42572;42573	chr2:178634435;178634434;178634433	chr2:179499162;179499161;179499160
N2AB	12475	37648;37649;37650	chr2:178634435;178634434;178634433	chr2:179499162;179499161;179499160
N2A	11548	34867;34868;34869	chr2:178634435;178634434;178634433	chr2:179499162;179499161;179499160
N2B	5051	15376;15377;15378	chr2:178634435;178634434;178634433	chr2:179499162;179499161;179499160
Novex-1	5176	15751;15752;15753	chr2:178634435;178634434;178634433	chr2:179499162;179499161;179499160
Novex-2	5243	15952;15953;15954	chr2:178634435;178634434;178634433	chr2:179499162;179499161;179499160
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-91
• Domain position: 63
• Structural Position: 146
• Q(SASA): 0.5328
• 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
F/L	None	None	0.999	N	0.461	0.365	0.21737058555	gnomAD-4.0.0	1.59277E-06	None	None	None	None	I	None	0	0	None	0	2.78164E-05	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
F/A	0.9013	likely_pathogenic	0.7236	pathogenic	-1.418	Destabilizing	1.0	D	0.562	neutral	None	None	None	None	I
F/C	0.8841	likely_pathogenic	0.7471	pathogenic	-0.329	Destabilizing	1.0	D	0.669	neutral	N	0.517888626	None	None	I
F/D	0.9594	likely_pathogenic	0.8863	pathogenic	0.254	Stabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	I
F/E	0.961	likely_pathogenic	0.8974	pathogenic	0.241	Stabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	I
F/G	0.9645	likely_pathogenic	0.8971	pathogenic	-1.659	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I
F/H	0.8887	likely_pathogenic	0.787	pathogenic	-0.215	Destabilizing	1.0	D	0.672	neutral	None	None	None	None	I
F/I	0.673	likely_pathogenic	0.4629	ambiguous	-0.768	Destabilizing	1.0	D	0.597	neutral	N	0.443411675	None	None	I
F/K	0.9682	likely_pathogenic	0.9102	pathogenic	-0.313	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
F/L	0.9559	likely_pathogenic	0.905	pathogenic	-0.768	Destabilizing	0.999	D	0.461	neutral	N	0.434958331	None	None	I
F/M	0.8304	likely_pathogenic	0.685	pathogenic	-0.47	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	I
F/N	0.9089	likely_pathogenic	0.7963	pathogenic	-0.114	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
F/P	0.979	likely_pathogenic	0.9278	pathogenic	-0.968	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	I
F/Q	0.9548	likely_pathogenic	0.8903	pathogenic	-0.262	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	I
F/R	0.9431	likely_pathogenic	0.8645	pathogenic	0.282	Stabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	I
F/S	0.8857	likely_pathogenic	0.6963	pathogenic	-0.845	Destabilizing	1.0	D	0.651	neutral	N	0.440309261	None	None	I
F/T	0.913	likely_pathogenic	0.7577	pathogenic	-0.766	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	I
F/V	0.7129	likely_pathogenic	0.5104	ambiguous	-0.968	Destabilizing	1.0	D	0.587	neutral	N	0.444284681	None	None	I
F/W	0.6906	likely_pathogenic	0.591	pathogenic	-0.51	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	I
F/Y	0.3091	likely_benign	0.2302	benign	-0.509	Destabilizing	0.999	D	0.463	neutral	N	0.445614709	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.