TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19030	57313;57314;57315	chr2:178598529;178598528;178598527	chr2:179463256;179463255;179463254
N2AB	17389	52390;52391;52392	chr2:178598529;178598528;178598527	chr2:179463256;179463255;179463254
N2A	16462	49609;49610;49611	chr2:178598529;178598528;178598527	chr2:179463256;179463255;179463254
N2B	9965	30118;30119;30120	chr2:178598529;178598528;178598527	chr2:179463256;179463255;179463254
Novex-1	10090	30493;30494;30495	chr2:178598529;178598528;178598527	chr2:179463256;179463255;179463254
Novex-2	10157	30694;30695;30696	chr2:178598529;178598528;178598527	chr2:179463256;179463255;179463254
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: Fn3-26
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.3592
• 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	rs1402903802	-0.779	0.997	N	0.43	0.127	0.336892272479	gnomAD-2.1.1	1.23E-05	None	None	None	None	N	None	0	0	None	0	0	None	3.46E-05	None	0	1.79E-05	0
E/D	rs1402903802	-0.779	0.997	N	0.43	0.127	0.336892272479	gnomAD-4.0.0	6.42224E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86875E-06	4.41826E-05	0
E/G	None	None	0.999	N	0.587	0.199	0.482209950775	gnomAD-4.0.0	6.86858E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00559E-07	0	0
E/K	rs966403005	None	0.997	N	0.473	0.298	0.413241256734	gnomAD-4.0.0	2.74775E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.60223E-06	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	0.1027	likely_benign	0.1071	benign	-0.658	Destabilizing	0.953	D	0.464	neutral	N	0.466359257	None	None	N
E/C	0.8331	likely_pathogenic	0.8325	pathogenic	-0.506	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
E/D	0.1531	likely_benign	0.1539	benign	-0.881	Destabilizing	0.997	D	0.43	neutral	N	0.492295065	None	None	N
E/F	0.694	likely_pathogenic	0.7176	pathogenic	0.112	Stabilizing	0.998	D	0.685	prob.neutral	None	None	None	None	N
E/G	0.1926	likely_benign	0.1947	benign	-1.01	Destabilizing	0.999	D	0.587	neutral	N	0.478155119	None	None	N
E/H	0.5655	likely_pathogenic	0.57	pathogenic	0.09	Stabilizing	1.0	D	0.456	neutral	None	None	None	None	N
E/I	0.197	likely_benign	0.205	benign	0.298	Stabilizing	0.469	N	0.476	neutral	None	None	None	None	N
E/K	0.2001	likely_benign	0.1968	benign	-0.39	Destabilizing	0.997	D	0.473	neutral	N	0.450581728	None	None	N
E/L	0.2793	likely_benign	0.301	benign	0.298	Stabilizing	0.931	D	0.573	neutral	None	None	None	None	N
E/M	0.3305	likely_benign	0.3373	benign	0.483	Stabilizing	0.998	D	0.661	neutral	None	None	None	None	N
E/N	0.2676	likely_benign	0.2765	benign	-1.011	Destabilizing	0.999	D	0.463	neutral	None	None	None	None	N
E/P	0.5557	ambiguous	0.5889	pathogenic	None	Stabilizing	0.999	D	0.522	neutral	None	None	None	None	N
E/Q	0.1769	likely_benign	0.1825	benign	-0.854	Destabilizing	0.999	D	0.474	neutral	N	0.470141017	None	None	N
E/R	0.3562	ambiguous	0.3525	ambiguous	0.021	Stabilizing	0.999	D	0.463	neutral	None	None	None	None	N
E/S	0.21	likely_benign	0.2151	benign	-1.257	Destabilizing	0.993	D	0.439	neutral	None	None	None	None	N
E/T	0.1885	likely_benign	0.2026	benign	-0.955	Destabilizing	0.985	D	0.511	neutral	None	None	None	None	N
E/V	0.1237	likely_benign	0.1252	benign	None	Stabilizing	0.219	N	0.397	neutral	N	0.463145594	None	None	N
E/W	0.8948	likely_pathogenic	0.902	pathogenic	0.422	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
E/Y	0.5824	likely_pathogenic	0.5973	pathogenic	0.38	Stabilizing	0.999	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.