TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13787	41584;41585;41586	chr2:178636212;178636211;178636210	chr2:179500939;179500938;179500937
N2AB	12146	36661;36662;36663	chr2:178636212;178636211;178636210	chr2:179500939;179500938;179500937
N2A	11219	33880;33881;33882	chr2:178636212;178636211;178636210	chr2:179500939;179500938;179500937
N2B	4722	14389;14390;14391	chr2:178636212;178636211;178636210	chr2:179500939;179500938;179500937
Novex-1	4847	14764;14765;14766	chr2:178636212;178636211;178636210	chr2:179500939;179500938;179500937
Novex-2	4914	14965;14966;14967	chr2:178636212;178636211;178636210	chr2:179500939;179500938;179500937
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: Ig-88
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.6758
• 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/Q	None	None	0.999	D	0.726	0.262	0.455909487837	gnomAD-4.0.0	1.64349E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.49651E-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	0.398	ambiguous	0.5356	ambiguous	-0.344	Destabilizing	0.998	D	0.743	deleterious	D	0.607782103	None	None	N
E/C	0.9688	likely_pathogenic	0.9803	pathogenic	-0.072	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
E/D	0.263	likely_benign	0.4072	ambiguous	-0.321	Destabilizing	0.434	N	0.249	neutral	N	0.513295134	None	None	N
E/F	0.9703	likely_pathogenic	0.9852	pathogenic	-0.124	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
E/G	0.3658	ambiguous	0.5039	ambiguous	-0.552	Destabilizing	0.999	D	0.706	prob.delet.	D	0.608917928	None	None	N
E/H	0.8613	likely_pathogenic	0.9222	pathogenic	0.097	Stabilizing	1.0	D	0.689	prob.delet.	None	None	None	None	N
E/I	0.8506	likely_pathogenic	0.9201	pathogenic	0.173	Stabilizing	1.0	D	0.733	deleterious	None	None	None	None	N
E/K	0.4632	ambiguous	0.6405	pathogenic	0.395	Stabilizing	0.998	D	0.669	prob.neutral	N	0.515594935	None	None	N
E/L	0.782	likely_pathogenic	0.8665	pathogenic	0.173	Stabilizing	1.0	D	0.726	deleterious	None	None	None	None	N
E/M	0.8551	likely_pathogenic	0.914	pathogenic	0.222	Stabilizing	1.0	D	0.733	deleterious	None	None	None	None	N
E/N	0.6322	likely_pathogenic	0.8026	pathogenic	-0.033	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
E/P	0.7693	likely_pathogenic	0.8105	pathogenic	0.021	Stabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
E/Q	0.3372	likely_benign	0.4496	ambiguous	0.027	Stabilizing	0.999	D	0.726	deleterious	D	0.522536008	None	None	N
E/R	0.6098	likely_pathogenic	0.7331	pathogenic	0.591	Stabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
E/S	0.4902	ambiguous	0.6429	pathogenic	-0.171	Destabilizing	0.997	D	0.665	prob.neutral	None	None	None	None	N
E/T	0.5863	likely_pathogenic	0.7356	pathogenic	0.008	Stabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
E/V	0.6332	likely_pathogenic	0.7577	pathogenic	0.021	Stabilizing	1.0	D	0.736	deleterious	D	0.585618011	None	None	N
E/W	0.9841	likely_pathogenic	0.9913	pathogenic	0.055	Stabilizing	1.0	D	0.728	deleterious	None	None	None	None	N
E/Y	0.9315	likely_pathogenic	0.9664	pathogenic	0.13	Stabilizing	1.0	D	0.717	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.