TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23695	71308;71309;71310	chr2:178575049;178575048;178575047	chr2:179439776;179439775;179439774
N2AB	22054	66385;66386;66387	chr2:178575049;178575048;178575047	chr2:179439776;179439775;179439774
N2A	21127	63604;63605;63606	chr2:178575049;178575048;178575047	chr2:179439776;179439775;179439774
N2B	14630	44113;44114;44115	chr2:178575049;178575048;178575047	chr2:179439776;179439775;179439774
Novex-1	14755	44488;44489;44490	chr2:178575049;178575048;178575047	chr2:179439776;179439775;179439774
Novex-2	14822	44689;44690;44691	chr2:178575049;178575048;178575047	chr2:179439776;179439775;179439774
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-130
• Domain position: 59
• Structural Position: 143
• Q(SASA): 0.7023
• 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/D	rs1709558707	None	0.825	N	0.457	0.096	0.215869574891	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/D	rs1709558707	None	0.825	N	0.457	0.096	0.215869574891	gnomAD-4.0.0	6.57419E-06	None	None	None	None	N	None	2.41208E-05	0	None	0	0	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
E/A	0.3356	likely_benign	0.3764	ambiguous	-0.461	Destabilizing	0.958	D	0.567	neutral	N	0.474967593	None	None	N
E/C	0.9269	likely_pathogenic	0.9463	pathogenic	0.118	Stabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
E/D	0.1409	likely_benign	0.1543	benign	-0.458	Destabilizing	0.825	D	0.457	neutral	N	0.435811772	None	None	N
E/F	0.9154	likely_pathogenic	0.9396	pathogenic	-0.589	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
E/G	0.2715	likely_benign	0.313	benign	-0.673	Destabilizing	0.919	D	0.541	neutral	N	0.465019958	None	None	N
E/H	0.7049	likely_pathogenic	0.7559	pathogenic	-0.675	Destabilizing	0.995	D	0.612	neutral	None	None	None	None	N
E/I	0.7857	likely_pathogenic	0.8158	pathogenic	0.065	Stabilizing	0.995	D	0.71	prob.delet.	None	None	None	None	N
E/K	0.377	ambiguous	0.4188	ambiguous	0.134	Stabilizing	0.958	D	0.521	neutral	N	0.415764574	None	None	N
E/L	0.7654	likely_pathogenic	0.8074	pathogenic	0.065	Stabilizing	0.995	D	0.672	neutral	None	None	None	None	N
E/M	0.7569	likely_pathogenic	0.8072	pathogenic	0.437	Stabilizing	1.0	D	0.633	neutral	None	None	None	None	N
E/N	0.3401	ambiguous	0.3923	ambiguous	-0.034	Destabilizing	0.18	N	0.325	neutral	None	None	None	None	N
E/P	0.9428	likely_pathogenic	0.9535	pathogenic	-0.09	Destabilizing	0.998	D	0.599	neutral	None	None	None	None	N
E/Q	0.2696	likely_benign	0.2992	benign	-0.015	Destabilizing	0.988	D	0.587	neutral	N	0.467868262	None	None	N
E/R	0.5359	ambiguous	0.588	pathogenic	0.192	Stabilizing	0.991	D	0.602	neutral	None	None	None	None	N
E/S	0.3246	likely_benign	0.3712	ambiguous	-0.237	Destabilizing	0.938	D	0.533	neutral	None	None	None	None	N
E/T	0.5	ambiguous	0.5432	ambiguous	-0.074	Destabilizing	0.991	D	0.585	neutral	None	None	None	None	N
E/V	0.6015	likely_pathogenic	0.645	pathogenic	-0.09	Destabilizing	0.994	D	0.63	neutral	N	0.496036298	None	None	N
E/W	0.9743	likely_pathogenic	0.9817	pathogenic	-0.524	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
E/Y	0.8013	likely_pathogenic	0.8484	pathogenic	-0.375	Destabilizing	0.998	D	0.657	neutral	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.