TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18011	54256;54257;54258	chr2:178605146;178605145;178605144	chr2:179469873;179469872;179469871
N2AB	16370	49333;49334;49335	chr2:178605146;178605145;178605144	chr2:179469873;179469872;179469871
N2A	15443	46552;46553;46554	chr2:178605146;178605145;178605144	chr2:179469873;179469872;179469871
N2B	8946	27061;27062;27063	chr2:178605146;178605145;178605144	chr2:179469873;179469872;179469871
Novex-1	9071	27436;27437;27438	chr2:178605146;178605145;178605144	chr2:179469873;179469872;179469871
Novex-2	9138	27637;27638;27639	chr2:178605146;178605145;178605144	chr2:179469873;179469872;179469871
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-114
• Domain position: 44
• Structural Position: 74
• Q(SASA): 0.4316
• 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
T/A	rs766446275	-0.145	0.76	N	0.409	0.071	0.225215365344	gnomAD-2.1.1	8.09E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.79E-05	0
T/A	rs766446275	-0.145	0.76	N	0.409	0.071	0.225215365344	gnomAD-4.0.0	1.23236E-05	None	None	None	None	N	None	0	2.23874E-05	None	0	0	None	0	0	1.52976E-05	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
T/A	0.0865	likely_benign	0.084	benign	-0.257	Destabilizing	0.76	D	0.409	neutral	N	0.485125872	None	None	N
T/C	0.3836	ambiguous	0.3939	ambiguous	-0.241	Destabilizing	0.999	D	0.451	neutral	None	None	None	None	N
T/D	0.2018	likely_benign	0.2104	benign	0.058	Stabilizing	0.986	D	0.417	neutral	None	None	None	None	N
T/E	0.279	likely_benign	0.2829	benign	-0.017	Destabilizing	0.986	D	0.402	neutral	None	None	None	None	N
T/F	0.3903	ambiguous	0.3884	ambiguous	-0.732	Destabilizing	0.993	D	0.594	neutral	None	None	None	None	N
T/G	0.1191	likely_benign	0.118	benign	-0.39	Destabilizing	0.91	D	0.487	neutral	None	None	None	None	N
T/H	0.2841	likely_benign	0.3004	benign	-0.664	Destabilizing	0.999	D	0.571	neutral	None	None	None	None	N
T/I	0.2939	likely_benign	0.3069	benign	-0.028	Destabilizing	0.885	D	0.395	neutral	N	0.461465786	None	None	N
T/K	0.1941	likely_benign	0.2086	benign	-0.406	Destabilizing	0.986	D	0.407	neutral	None	None	None	None	N
T/L	0.1457	likely_benign	0.1479	benign	-0.028	Destabilizing	0.91	D	0.381	neutral	None	None	None	None	N
T/M	0.1537	likely_benign	0.1502	benign	0.05	Stabilizing	0.998	D	0.426	neutral	None	None	None	None	N
T/N	0.0902	likely_benign	0.0907	benign	-0.177	Destabilizing	0.982	D	0.403	neutral	N	0.454456248	None	None	N
T/P	0.2395	likely_benign	0.2476	benign	-0.075	Destabilizing	0.991	D	0.43	neutral	N	0.492918635	None	None	N
T/Q	0.2495	likely_benign	0.2526	benign	-0.391	Destabilizing	0.993	D	0.413	neutral	None	None	None	None	N
T/R	0.2097	likely_benign	0.2153	benign	-0.12	Destabilizing	0.986	D	0.42	neutral	None	None	None	None	N
T/S	0.0741	likely_benign	0.0702	benign	-0.351	Destabilizing	0.17	N	0.291	neutral	N	0.431576601	None	None	N
T/V	0.1934	likely_benign	0.1998	benign	-0.075	Destabilizing	0.214	N	0.289	neutral	None	None	None	None	N
T/W	0.6686	likely_pathogenic	0.674	pathogenic	-0.775	Destabilizing	0.999	D	0.622	neutral	None	None	None	None	N
T/Y	0.3952	ambiguous	0.406	ambiguous	-0.485	Destabilizing	0.998	D	0.584	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.