TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19225	57898;57899;57900	chr2:178595681;178595680;178595679	chr2:179460408;179460407;179460406
N2AB	17584	52975;52976;52977	chr2:178595681;178595680;178595679	chr2:179460408;179460407;179460406
N2A	16657	50194;50195;50196	chr2:178595681;178595680;178595679	chr2:179460408;179460407;179460406
N2B	10160	30703;30704;30705	chr2:178595681;178595680;178595679	chr2:179460408;179460407;179460406
Novex-1	10285	31078;31079;31080	chr2:178595681;178595680;178595679	chr2:179460408;179460407;179460406
Novex-2	10352	31279;31280;31281	chr2:178595681;178595680;178595679	chr2:179460408;179460407;179460406
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-27
• Domain position: 43
• Structural Position: 44
• Q(SASA): 0.107
• 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
E/K	rs2051373830	None	0.994	N	0.562	0.401	0.486209434461	gnomAD-4.0.0	3.20906E-06	None	None	None	None	N	None	0	2.3175E-05	None	0	0	None	0	0	0	1.46066E-05	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
E/A	0.3957	ambiguous	0.5757	pathogenic	-0.913	Destabilizing	0.989	D	0.518	neutral	N	0.470105018	None	None	N
E/C	0.9552	likely_pathogenic	0.9758	pathogenic	-0.585	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
E/D	0.2895	likely_benign	0.3005	benign	-1.447	Destabilizing	0.217	N	0.429	neutral	N	0.475192171	None	None	N
E/F	0.9464	likely_pathogenic	0.9747	pathogenic	-0.4	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
E/G	0.5779	likely_pathogenic	0.7072	pathogenic	-1.313	Destabilizing	0.994	D	0.633	neutral	N	0.488235726	None	None	N
E/H	0.8536	likely_pathogenic	0.9308	pathogenic	-0.777	Destabilizing	1.0	D	0.654	neutral	None	None	None	None	N
E/I	0.7161	likely_pathogenic	0.8486	pathogenic	0.188	Stabilizing	0.995	D	0.711	prob.delet.	None	None	None	None	N
E/K	0.6528	likely_pathogenic	0.8287	pathogenic	-0.916	Destabilizing	0.994	D	0.562	neutral	N	0.505128289	None	None	N
E/L	0.6979	likely_pathogenic	0.8402	pathogenic	0.188	Stabilizing	0.983	D	0.663	neutral	None	None	None	None	N
E/M	0.7618	likely_pathogenic	0.8815	pathogenic	0.745	Stabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
E/N	0.7047	likely_pathogenic	0.7967	pathogenic	-1.392	Destabilizing	0.998	D	0.637	neutral	None	None	None	None	N
E/P	0.8279	likely_pathogenic	0.9033	pathogenic	-0.157	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
E/Q	0.3629	ambiguous	0.5482	ambiguous	-1.221	Destabilizing	0.998	D	0.637	neutral	N	0.515363926	None	None	N
E/R	0.7595	likely_pathogenic	0.8767	pathogenic	-0.674	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
E/S	0.6034	likely_pathogenic	0.7391	pathogenic	-1.76	Destabilizing	0.992	D	0.571	neutral	None	None	None	None	N
E/T	0.6694	likely_pathogenic	0.803	pathogenic	-1.422	Destabilizing	0.992	D	0.645	neutral	None	None	None	None	N
E/V	0.5294	ambiguous	0.6995	pathogenic	-0.157	Destabilizing	0.733	D	0.425	neutral	N	0.491362825	None	None	N
E/W	0.9851	likely_pathogenic	0.9937	pathogenic	-0.216	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
E/Y	0.9217	likely_pathogenic	0.9648	pathogenic	-0.166	Destabilizing	1.0	D	0.726	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.