TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15335	46228;46229;46230	chr2:178620518;178620517;178620516	chr2:179485245;179485244;179485243
N2AB	13694	41305;41306;41307	chr2:178620518;178620517;178620516	chr2:179485245;179485244;179485243
N2A	12767	38524;38525;38526	chr2:178620518;178620517;178620516	chr2:179485245;179485244;179485243
N2B	6270	19033;19034;19035	chr2:178620518;178620517;178620516	chr2:179485245;179485244;179485243
Novex-1	6395	19408;19409;19410	chr2:178620518;178620517;178620516	chr2:179485245;179485244;179485243
Novex-2	6462	19609;19610;19611	chr2:178620518;178620517;178620516	chr2:179485245;179485244;179485243
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-105
• Domain position: 34
• Structural Position: 49
• Q(SASA): 0.0893
• 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
T/I	None	None	0.027	N	0.662	0.093	0.227260227426	gnomAD-4.0.0	1.59441E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86402E-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
T/A	0.1371	likely_benign	0.1193	benign	-1.084	Destabilizing	0.027	N	0.598	neutral	N	0.454218079	None	None	N
T/C	0.3927	ambiguous	0.4537	ambiguous	-0.816	Destabilizing	0.935	D	0.661	neutral	None	None	None	None	N
T/D	0.549	ambiguous	0.4844	ambiguous	-1.184	Destabilizing	0.555	D	0.709	prob.delet.	None	None	None	None	N
T/E	0.2626	likely_benign	0.2496	benign	-1.022	Destabilizing	0.262	N	0.697	prob.neutral	None	None	None	None	N
T/F	0.2497	likely_benign	0.249	benign	-0.79	Destabilizing	0.235	N	0.7	prob.neutral	None	None	None	None	N
T/G	0.3623	ambiguous	0.3413	ambiguous	-1.473	Destabilizing	0.149	N	0.68	prob.neutral	None	None	None	None	N
T/H	0.2673	likely_benign	0.2705	benign	-1.661	Destabilizing	0.935	D	0.657	neutral	None	None	None	None	N
T/I	0.2174	likely_benign	0.194	benign	-0.08	Destabilizing	0.027	N	0.662	neutral	N	0.443902459	None	None	N
T/K	0.2089	likely_benign	0.1915	benign	-0.605	Destabilizing	0.149	N	0.679	prob.neutral	None	None	None	None	N
T/L	0.1097	likely_benign	0.1046	benign	-0.08	Destabilizing	None	N	0.401	neutral	None	None	None	None	N
T/M	0.0793	likely_benign	0.0803	benign	-0.08	Destabilizing	0.001	N	0.386	neutral	None	None	None	None	N
T/N	0.1839	likely_benign	0.1596	benign	-1.125	Destabilizing	0.484	N	0.705	prob.neutral	N	0.447652384	None	None	N
T/P	0.9052	likely_pathogenic	0.7721	pathogenic	-0.382	Destabilizing	0.741	D	0.701	prob.neutral	N	0.448839916	None	None	N
T/Q	0.1727	likely_benign	0.1755	benign	-0.986	Destabilizing	0.38	N	0.699	prob.neutral	None	None	None	None	N
T/R	0.1664	likely_benign	0.1411	benign	-0.753	Destabilizing	0.38	N	0.714	prob.delet.	None	None	None	None	N
T/S	0.1487	likely_benign	0.1429	benign	-1.358	Destabilizing	0.117	N	0.623	neutral	N	0.433099472	None	None	N
T/V	0.1716	likely_benign	0.1768	benign	-0.382	Destabilizing	0.035	N	0.549	neutral	None	None	None	None	N
T/W	0.5144	ambiguous	0.5147	ambiguous	-0.89	Destabilizing	0.935	D	0.663	neutral	None	None	None	None	N
T/Y	0.2663	likely_benign	0.2748	benign	-0.535	Destabilizing	0.555	D	0.689	prob.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.