TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24405	73438;73439;73440	chr2:178572919;178572918;178572917	chr2:179437646;179437645;179437644
N2AB	22764	68515;68516;68517	chr2:178572919;178572918;178572917	chr2:179437646;179437645;179437644
N2A	21837	65734;65735;65736	chr2:178572919;178572918;178572917	chr2:179437646;179437645;179437644
N2B	15340	46243;46244;46245	chr2:178572919;178572918;178572917	chr2:179437646;179437645;179437644
Novex-1	15465	46618;46619;46620	chr2:178572919;178572918;178572917	chr2:179437646;179437645;179437644
Novex-2	15532	46819;46820;46821	chr2:178572919;178572918;178572917	chr2:179437646;179437645;179437644
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: Fn3-65
• Domain position: 83
• Structural Position: 114
• Q(SASA): 0.4668
• Predicted PPI site: I

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	rs1027579307	0.003	0.981	N	0.506	0.21	0.252681307341	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
E/D	rs1027579307	0.003	0.981	N	0.506	0.21	0.252681307341	gnomAD-4.0.0	1.59222E-06	None	None	None	None	I	None	0	2.28728E-05	None	0	0	None	0	0	0	0	0
E/K	rs764485436	0.746	0.989	N	0.601	0.369	0.365703291355	gnomAD-2.1.1	3.23E-05	None	None	None	None	I	None	0	5.81E-05	None	0	2.81658E-04	None	0	None	0	8.93E-06	0
E/K	rs764485436	0.746	0.989	N	0.601	0.369	0.365703291355	gnomAD-4.0.0	1.02659E-05	None	None	None	None	I	None	0	4.47407E-05	None	0	1.01199E-04	None	0	0	5.39758E-06	2.31889E-05	1.65739E-05

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	0.1358	likely_benign	0.15	benign	-0.269	Destabilizing	0.805	D	0.589	neutral	N	0.372390304	None	None	I
E/C	0.7983	likely_pathogenic	0.8031	pathogenic	0.065	Stabilizing	0.999	D	0.761	deleterious	None	None	None	None	I
E/D	0.4156	ambiguous	0.3993	ambiguous	-0.226	Destabilizing	0.981	D	0.506	neutral	N	0.489966836	None	None	I
E/F	0.8237	likely_pathogenic	0.8546	pathogenic	-0.275	Destabilizing	0.975	D	0.724	prob.delet.	None	None	None	None	I
E/G	0.2929	likely_benign	0.3098	benign	-0.415	Destabilizing	0.983	D	0.594	neutral	N	0.473477231	None	None	I
E/H	0.5875	likely_pathogenic	0.6302	pathogenic	0.077	Stabilizing	0.999	D	0.568	neutral	None	None	None	None	I
E/I	0.3402	ambiguous	0.3692	ambiguous	0.068	Stabilizing	0.845	D	0.651	neutral	None	None	None	None	I
E/K	0.1893	likely_benign	0.2168	benign	0.513	Stabilizing	0.989	D	0.601	neutral	N	0.476440178	None	None	I
E/L	0.5082	ambiguous	0.5235	ambiguous	0.068	Stabilizing	0.845	D	0.639	neutral	None	None	None	None	I
E/M	0.4654	ambiguous	0.4935	ambiguous	0.143	Stabilizing	0.997	D	0.696	prob.neutral	None	None	None	None	I
E/N	0.4624	ambiguous	0.4807	ambiguous	0.245	Stabilizing	0.996	D	0.579	neutral	None	None	None	None	I
E/P	0.9533	likely_pathogenic	0.9531	pathogenic	-0.025	Destabilizing	0.996	D	0.621	neutral	None	None	None	None	I
E/Q	0.1572	likely_benign	0.1748	benign	0.258	Stabilizing	0.998	D	0.544	neutral	N	0.469034203	None	None	I
E/R	0.3296	likely_benign	0.3699	ambiguous	0.651	Stabilizing	0.987	D	0.581	neutral	None	None	None	None	I
E/S	0.2928	likely_benign	0.3112	benign	0.1	Stabilizing	0.957	D	0.592	neutral	None	None	None	None	I
E/T	0.3409	ambiguous	0.355	ambiguous	0.226	Stabilizing	0.916	D	0.619	neutral	None	None	None	None	I
E/V	0.1928	likely_benign	0.2078	benign	-0.025	Destabilizing	0.025	N	0.449	neutral	N	0.39813411	None	None	I
E/W	0.9565	likely_pathogenic	0.9651	pathogenic	-0.169	Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	I
E/Y	0.722	likely_pathogenic	0.7663	pathogenic	-0.036	Destabilizing	0.987	D	0.701	prob.neutral	None	None	None	None	I

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.