TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23531	70816;70817;70818	chr2:178575541;178575540;178575539	chr2:179440268;179440267;179440266
N2AB	21890	65893;65894;65895	chr2:178575541;178575540;178575539	chr2:179440268;179440267;179440266
N2A	20963	63112;63113;63114	chr2:178575541;178575540;178575539	chr2:179440268;179440267;179440266
N2B	14466	43621;43622;43623	chr2:178575541;178575540;178575539	chr2:179440268;179440267;179440266
Novex-1	14591	43996;43997;43998	chr2:178575541;178575540;178575539	chr2:179440268;179440267;179440266
Novex-2	14658	44197;44198;44199	chr2:178575541;178575540;178575539	chr2:179440268;179440267;179440266
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: Fn3-58
• Domain position: 97
• Structural Position: 132
• Q(SASA): 0.62
• 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	rs1182129747	None	0.872	N	0.616	0.28	0.359357374593	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs1182129747	None	0.872	N	0.616	0.28	0.359357374593	gnomAD-4.0.0	2.03004E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.20497E-06	4.69836E-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	0.2976	likely_benign	0.3624	ambiguous	-0.041	Destabilizing	0.88	D	0.565	neutral	N	0.518435942	None	None	N
E/C	0.9413	likely_pathogenic	0.948	pathogenic	0.056	Stabilizing	0.999	D	0.871	deleterious	None	None	None	None	N
E/D	0.3973	ambiguous	0.4093	ambiguous	-0.257	Destabilizing	0.282	N	0.545	neutral	N	0.472607652	None	None	N
E/F	0.9463	likely_pathogenic	0.9616	pathogenic	-0.107	Destabilizing	0.997	D	0.749	deleterious	None	None	None	None	N
E/G	0.4109	ambiguous	0.4776	ambiguous	-0.169	Destabilizing	0.98	D	0.497	neutral	N	0.469248282	None	None	N
E/H	0.8337	likely_pathogenic	0.8883	pathogenic	0.335	Stabilizing	0.989	D	0.436	neutral	None	None	None	None	N
E/I	0.7509	likely_pathogenic	0.8121	pathogenic	0.239	Stabilizing	0.995	D	0.803	deleterious	None	None	None	None	N
E/K	0.3875	ambiguous	0.4954	ambiguous	0.581	Stabilizing	0.872	D	0.616	neutral	N	0.495470066	None	None	N
E/L	0.7379	likely_pathogenic	0.8029	pathogenic	0.239	Stabilizing	0.967	D	0.559	neutral	None	None	None	None	N
E/M	0.6493	likely_pathogenic	0.7249	pathogenic	0.156	Stabilizing	0.992	D	0.69	prob.delet.	None	None	None	None	N
E/N	0.6344	likely_pathogenic	0.6915	pathogenic	0.349	Stabilizing	0.965	D	0.509	neutral	None	None	None	None	N
E/P	0.9889	likely_pathogenic	0.993	pathogenic	0.164	Stabilizing	0.965	D	0.581	neutral	None	None	None	None	N
E/Q	0.1858	likely_benign	0.2372	benign	0.353	Stabilizing	0.275	N	0.193	neutral	N	0.497140737	None	None	N
E/R	0.579	likely_pathogenic	0.6897	pathogenic	0.721	Stabilizing	0.948	D	0.528	neutral	None	None	None	None	N
E/S	0.4111	ambiguous	0.4889	ambiguous	0.217	Stabilizing	0.907	D	0.507	neutral	None	None	None	None	N
E/T	0.4742	ambiguous	0.5662	pathogenic	0.327	Stabilizing	0.965	D	0.549	neutral	None	None	None	None	N
E/V	0.4844	ambiguous	0.5604	ambiguous	0.164	Stabilizing	0.97	D	0.461	neutral	N	0.495216577	None	None	N
E/W	0.9887	likely_pathogenic	0.9926	pathogenic	-0.056	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
E/Y	0.9282	likely_pathogenic	0.947	pathogenic	0.125	Stabilizing	0.999	D	0.755	deleterious	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.