TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31064	93415;93416;93417	chr2:178548436;178548435;178548434	chr2:179413163;179413162;179413161
N2AB	29423	88492;88493;88494	chr2:178548436;178548435;178548434	chr2:179413163;179413162;179413161
N2A	28496	85711;85712;85713	chr2:178548436;178548435;178548434	chr2:179413163;179413162;179413161
N2B	21999	66220;66221;66222	chr2:178548436;178548435;178548434	chr2:179413163;179413162;179413161
Novex-1	22124	66595;66596;66597	chr2:178548436;178548435;178548434	chr2:179413163;179413162;179413161
Novex-2	22191	66796;66797;66798	chr2:178548436;178548435;178548434	chr2:179413163;179413162;179413161
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Fn3-114
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.5566
• 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
Q/H	None	None	0.999	N	0.562	0.214	0.202949470691	gnomAD-4.0.0	2.16058E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.3625E-05	0	0
Q/P	None	None	0.999	N	0.558	0.503	0.433600339574	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	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
Q/A	0.2048	likely_benign	0.2055	benign	-0.479	Destabilizing	0.964	D	0.553	neutral	None	None	None	None	N
Q/C	0.6548	likely_pathogenic	0.6271	pathogenic	-0.048	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
Q/D	0.5469	ambiguous	0.4471	ambiguous	-0.008	Destabilizing	0.993	D	0.531	neutral	None	None	None	None	N
Q/E	0.1108	likely_benign	0.1005	benign	0.058	Stabilizing	0.977	D	0.499	neutral	N	0.470709071	None	None	N
Q/F	0.766	likely_pathogenic	0.7281	pathogenic	-0.243	Destabilizing	0.999	D	0.64	neutral	None	None	None	None	N
Q/G	0.3421	ambiguous	0.3239	benign	-0.787	Destabilizing	0.993	D	0.516	neutral	None	None	None	None	N
Q/H	0.2242	likely_benign	0.1922	benign	-0.463	Destabilizing	0.999	D	0.562	neutral	N	0.467207406	None	None	N
Q/I	0.3431	ambiguous	0.3409	ambiguous	0.285	Stabilizing	0.996	D	0.637	neutral	None	None	None	None	N
Q/K	0.157	likely_benign	0.1325	benign	-0.154	Destabilizing	0.99	D	0.551	neutral	N	0.406849594	None	None	N
Q/L	0.1288	likely_benign	0.1263	benign	0.285	Stabilizing	0.98	D	0.507	neutral	N	0.462916307	None	None	N
Q/M	0.3035	likely_benign	0.3055	benign	0.429	Stabilizing	0.999	D	0.563	neutral	None	None	None	None	N
Q/N	0.2965	likely_benign	0.2627	benign	-0.676	Destabilizing	0.993	D	0.528	neutral	None	None	None	None	N
Q/P	0.6955	likely_pathogenic	0.6572	pathogenic	0.061	Stabilizing	0.999	D	0.558	neutral	N	0.473561285	None	None	N
Q/R	0.1956	likely_benign	0.1601	benign	-0.032	Destabilizing	0.99	D	0.561	neutral	N	0.452776672	None	None	N
Q/S	0.2413	likely_benign	0.2258	benign	-0.763	Destabilizing	0.971	D	0.541	neutral	None	None	None	None	N
Q/T	0.16	likely_benign	0.1579	benign	-0.508	Destabilizing	0.469	N	0.231	neutral	None	None	None	None	N
Q/V	0.2046	likely_benign	0.2073	benign	0.061	Stabilizing	0.985	D	0.52	neutral	None	None	None	None	N
Q/W	0.7536	likely_pathogenic	0.7029	pathogenic	-0.123	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
Q/Y	0.5749	likely_pathogenic	0.5146	ambiguous	0.093	Stabilizing	0.999	D	0.585	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.