TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34194	102805;102806;102807	chr2:178534035;178534034;178534033	chr2:179398762;179398761;179398760
N2AB	32553	97882;97883;97884	chr2:178534035;178534034;178534033	chr2:179398762;179398761;179398760
N2A	31626	95101;95102;95103	chr2:178534035;178534034;178534033	chr2:179398762;179398761;179398760
N2B	25129	75610;75611;75612	chr2:178534035;178534034;178534033	chr2:179398762;179398761;179398760
Novex-1	25254	75985;75986;75987	chr2:178534035;178534034;178534033	chr2:179398762;179398761;179398760
Novex-2	25321	76186;76187;76188	chr2:178534035;178534034;178534033	chr2:179398762;179398761;179398760
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-160
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.0747
• 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
L/I	rs745744350	-0.594	None	N	0.296	0.179	0.549121438896	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.86E-06	0
L/I	rs745744350	-0.594	None	N	0.296	0.179	0.549121438896	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/I	rs745744350	-0.594	None	N	0.296	0.179	0.549121438896	gnomAD-4.0.0	6.08965E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.02465E-06	0	3.40275E-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
L/A	0.7729	likely_pathogenic	0.736	pathogenic	-2.555	Highly Destabilizing	0.035	N	0.721	prob.delet.	None	None	None	None	N
L/C	0.7977	likely_pathogenic	0.7865	pathogenic	-1.513	Destabilizing	0.935	D	0.801	deleterious	None	None	None	None	N
L/D	0.9978	likely_pathogenic	0.9976	pathogenic	-3.206	Highly Destabilizing	0.555	D	0.863	deleterious	None	None	None	None	N
L/E	0.9823	likely_pathogenic	0.9776	pathogenic	-2.897	Highly Destabilizing	0.555	D	0.85	deleterious	None	None	None	None	N
L/F	0.5481	ambiguous	0.5422	ambiguous	-1.592	Destabilizing	0.317	N	0.696	prob.neutral	N	0.515938082	None	None	N
L/G	0.9558	likely_pathogenic	0.9451	pathogenic	-3.104	Highly Destabilizing	0.38	N	0.842	deleterious	None	None	None	None	N
L/H	0.9632	likely_pathogenic	0.9593	pathogenic	-2.933	Highly Destabilizing	0.915	D	0.865	deleterious	D	0.529322304	None	None	N
L/I	0.2373	likely_benign	0.226	benign	-0.875	Destabilizing	None	N	0.296	neutral	N	0.516884944	None	None	N
L/K	0.9597	likely_pathogenic	0.9505	pathogenic	-1.996	Destabilizing	0.38	N	0.829	deleterious	None	None	None	None	N
L/M	0.1046	likely_benign	0.0929	benign	-1.039	Destabilizing	0.002	N	0.418	neutral	None	None	None	None	N
L/N	0.9758	likely_pathogenic	0.9727	pathogenic	-2.797	Highly Destabilizing	0.555	D	0.868	deleterious	None	None	None	None	N
L/P	0.993	likely_pathogenic	0.9925	pathogenic	-1.431	Destabilizing	0.741	D	0.866	deleterious	D	0.529322304	None	None	N
L/Q	0.9025	likely_pathogenic	0.8777	pathogenic	-2.366	Highly Destabilizing	0.38	N	0.856	deleterious	None	None	None	None	N
L/R	0.9504	likely_pathogenic	0.9427	pathogenic	-2.262	Highly Destabilizing	0.317	N	0.852	deleterious	D	0.529322304	None	None	N
L/S	0.942	likely_pathogenic	0.9331	pathogenic	-3.156	Highly Destabilizing	0.149	N	0.829	deleterious	None	None	None	None	N
L/T	0.8582	likely_pathogenic	0.8318	pathogenic	-2.69	Highly Destabilizing	0.149	N	0.753	deleterious	None	None	None	None	N
L/V	0.2577	likely_benign	0.2491	benign	-1.431	Destabilizing	0.004	N	0.487	neutral	N	0.504670682	None	None	N
L/W	0.9535	likely_pathogenic	0.9518	pathogenic	-1.858	Destabilizing	0.935	D	0.854	deleterious	None	None	None	None	N
L/Y	0.9499	likely_pathogenic	0.9476	pathogenic	-1.768	Destabilizing	0.555	D	0.799	deleterious	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.