TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28897	86914;86915;86916	chr2:178559443;178559442;178559441	chr2:179424170;179424169;179424168
N2AB	27256	81991;81992;81993	chr2:178559443;178559442;178559441	chr2:179424170;179424169;179424168
N2A	26329	79210;79211;79212	chr2:178559443;178559442;178559441	chr2:179424170;179424169;179424168
N2B	19832	59719;59720;59721	chr2:178559443;178559442;178559441	chr2:179424170;179424169;179424168
Novex-1	19957	60094;60095;60096	chr2:178559443;178559442;178559441	chr2:179424170;179424169;179424168
Novex-2	20024	60295;60296;60297	chr2:178559443;178559442;178559441	chr2:179424170;179424169;179424168
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-98
• Domain position: 53
• Structural Position: 70
• Q(SASA): 0.4561
• 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
N/H	rs1702786623	None	0.896	N	0.373	0.176	0.186928172975	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
N/H	rs1702786623	None	0.896	N	0.373	0.176	0.186928172975	gnomAD-4.0.0	6.57056E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46977E-05	0	0
N/K	rs756448014	0.472	0.201	N	0.205	0.073	0.0806252709748	gnomAD-2.1.1	8.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.77E-05	0
N/K	rs756448014	0.472	0.201	N	0.205	0.073	0.0806252709748	gnomAD-4.0.0	3.42125E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49763E-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
N/A	0.1258	likely_benign	0.1391	benign	-0.475	Destabilizing	0.25	N	0.279	neutral	None	None	None	None	N
N/C	0.1749	likely_benign	0.1963	benign	0.454	Stabilizing	0.992	D	0.34	neutral	None	None	None	None	N
N/D	0.1122	likely_benign	0.1149	benign	-0.623	Destabilizing	0.002	N	0.103	neutral	N	0.384839526	None	None	N
N/E	0.3064	likely_benign	0.3254	benign	-0.639	Destabilizing	0.002	N	0.121	neutral	None	None	None	None	N
N/F	0.4936	ambiguous	0.5273	ambiguous	-0.767	Destabilizing	0.92	D	0.353	neutral	None	None	None	None	N
N/G	0.1498	likely_benign	0.1615	benign	-0.686	Destabilizing	0.25	N	0.265	neutral	None	None	None	None	N
N/H	0.1028	likely_benign	0.1065	benign	-0.783	Destabilizing	0.896	D	0.373	neutral	N	0.457355772	None	None	N
N/I	0.2136	likely_benign	0.2374	benign	0.01	Stabilizing	0.896	D	0.384	neutral	N	0.456910268	None	None	N
N/K	0.2717	likely_benign	0.2864	benign	0.003	Stabilizing	0.201	N	0.205	neutral	N	0.430977247	None	None	N
N/L	0.2252	likely_benign	0.2441	benign	0.01	Stabilizing	0.617	D	0.357	neutral	None	None	None	None	N
N/M	0.2982	likely_benign	0.3267	benign	0.705	Stabilizing	0.992	D	0.295	neutral	None	None	None	None	N
N/P	0.348	ambiguous	0.3801	ambiguous	-0.125	Destabilizing	0.92	D	0.335	neutral	None	None	None	None	N
N/Q	0.2537	likely_benign	0.2716	benign	-0.6	Destabilizing	0.447	N	0.296	neutral	None	None	None	None	N
N/R	0.281	likely_benign	0.2945	benign	0.161	Stabilizing	0.617	D	0.293	neutral	None	None	None	None	N
N/S	0.0609	likely_benign	0.0634	benign	-0.244	Destabilizing	0.007	N	0.113	neutral	N	0.415450435	None	None	N
N/T	0.0951	likely_benign	0.1055	benign	-0.121	Destabilizing	0.201	N	0.197	neutral	N	0.387013039	None	None	N
N/V	0.1846	likely_benign	0.2039	benign	-0.125	Destabilizing	0.617	D	0.34	neutral	None	None	None	None	N
N/W	0.6808	likely_pathogenic	0.6985	pathogenic	-0.686	Destabilizing	0.992	D	0.481	neutral	None	None	None	None	N
N/Y	0.1723	likely_benign	0.1786	benign	-0.428	Destabilizing	0.963	D	0.319	neutral	N	0.471631791	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.