TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5229	15910;15911;15912	chr2:178733704;178733703;178733702	chr2:179598431;179598430;179598429
N2AB	4912	14959;14960;14961	chr2:178733704;178733703;178733702	chr2:179598431;179598430;179598429
N2A	3985	12178;12179;12180	chr2:178733704;178733703;178733702	chr2:179598431;179598430;179598429
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-35
• Domain position: 62
• Structural Position: 143
• Q(SASA): 0.6258
• 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
D/A	rs373355675	-0.235	0.051	N	0.217	0.167	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
D/A	rs373355675	-0.235	0.051	N	0.217	0.167	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.82E-05	0	0	0	0	None	0	0	0	0	0
D/A	rs373355675	-0.235	0.051	N	0.217	0.167	None	gnomAD-4.0.0	3.84297E-06	None	None	None	None	N	None	5.07288E-05	0	None	0	0	None	0	0	0	0	0
D/H	None	None	0.966	N	0.351	0.201	0.241664281697	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
D/A	0.1031	likely_benign	0.1294	benign	-0.408	Destabilizing	0.051	N	0.217	neutral	N	0.448130819	None	None	N
D/C	0.4304	ambiguous	0.5617	ambiguous	0.007	Stabilizing	0.998	D	0.398	neutral	None	None	None	None	N
D/E	0.1061	likely_benign	0.129	benign	-0.393	Destabilizing	0.625	D	0.283	neutral	N	0.417194422	None	None	N
D/F	0.42	ambiguous	0.5248	ambiguous	-0.259	Destabilizing	0.991	D	0.42	neutral	None	None	None	None	N
D/G	0.1075	likely_benign	0.1365	benign	-0.643	Destabilizing	0.005	N	0.153	neutral	N	0.441650357	None	None	N
D/H	0.1598	likely_benign	0.2087	benign	-0.228	Destabilizing	0.966	D	0.351	neutral	N	0.458048444	None	None	N
D/I	0.2841	likely_benign	0.3934	ambiguous	0.174	Stabilizing	0.949	D	0.45	neutral	None	None	None	None	N
D/K	0.2097	likely_benign	0.2568	benign	0.25	Stabilizing	0.842	D	0.337	neutral	None	None	None	None	N
D/L	0.2861	likely_benign	0.3638	ambiguous	0.174	Stabilizing	0.842	D	0.42	neutral	None	None	None	None	N
D/M	0.428	ambiguous	0.5352	ambiguous	0.408	Stabilizing	0.998	D	0.394	neutral	None	None	None	None	N
D/N	0.0709	likely_benign	0.0792	benign	-0.171	Destabilizing	0.005	N	0.101	neutral	N	0.374986688	None	None	N
D/P	0.6467	likely_pathogenic	0.7576	pathogenic	0.003	Stabilizing	0.974	D	0.391	neutral	None	None	None	None	N
D/Q	0.1888	likely_benign	0.2349	benign	-0.105	Destabilizing	0.974	D	0.351	neutral	None	None	None	None	N
D/R	0.2232	likely_benign	0.2776	benign	0.39	Stabilizing	0.949	D	0.429	neutral	None	None	None	None	N
D/S	0.0871	likely_benign	0.1063	benign	-0.272	Destabilizing	0.525	D	0.329	neutral	None	None	None	None	N
D/T	0.1599	likely_benign	0.215	benign	-0.08	Destabilizing	0.029	N	0.159	neutral	None	None	None	None	N
D/V	0.1701	likely_benign	0.2316	benign	0.003	Stabilizing	0.801	D	0.421	neutral	N	0.45759062	None	None	N
D/W	0.774	likely_pathogenic	0.8536	pathogenic	-0.087	Destabilizing	0.998	D	0.474	neutral	None	None	None	None	N
D/Y	0.1729	likely_benign	0.2076	benign	-0.011	Destabilizing	0.989	D	0.416	neutral	N	0.448101598	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.