TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16041	48346;48347;48348	chr2:178616768;178616767;178616766	chr2:179481495;179481494;179481493
N2AB	14400	43423;43424;43425	chr2:178616768;178616767;178616766	chr2:179481495;179481494;179481493
N2A	13473	40642;40643;40644	chr2:178616768;178616767;178616766	chr2:179481495;179481494;179481493
N2B	6976	21151;21152;21153	chr2:178616768;178616767;178616766	chr2:179481495;179481494;179481493
Novex-1	7101	21526;21527;21528	chr2:178616768;178616767;178616766	chr2:179481495;179481494;179481493
Novex-2	7168	21727;21728;21729	chr2:178616768;178616767;178616766	chr2:179481495;179481494;179481493
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-109
• Domain position: 74
• Structural Position: 163
• Q(SASA): 0.5604
• Predicted PPI site: I

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
V/M	rs2057419029	None	0.781	D	0.61	0.328	0.578523416491	gnomAD-4.0.0	1.36929E-06	None	None	None	None	I	None	2.99455E-05	0	None	0	0	None	0	0	8.99879E-07	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
V/A	0.3067	likely_benign	0.3038	benign	-0.332	Destabilizing	0.002	N	0.504	neutral	N	0.494019539	None	None	I
V/C	0.7158	likely_pathogenic	0.702	pathogenic	-0.767	Destabilizing	0.947	D	0.63	neutral	None	None	None	None	I
V/D	0.5552	ambiguous	0.5407	ambiguous	-0.361	Destabilizing	0.7	D	0.678	prob.neutral	None	None	None	None	I
V/E	0.4019	ambiguous	0.4011	ambiguous	-0.477	Destabilizing	0.638	D	0.647	neutral	D	0.551204473	None	None	I
V/F	0.2348	likely_benign	0.2167	benign	-0.721	Destabilizing	0.826	D	0.616	neutral	None	None	None	None	I
V/G	0.2746	likely_benign	0.2889	benign	-0.389	Destabilizing	0.468	N	0.6	neutral	D	0.591736491	None	None	I
V/H	0.6798	likely_pathogenic	0.6544	pathogenic	0.004	Stabilizing	0.982	D	0.685	prob.neutral	None	None	None	None	I
V/I	0.1083	likely_benign	0.0973	benign	-0.321	Destabilizing	0.009	N	0.499	neutral	None	None	None	None	I
V/K	0.5117	ambiguous	0.4832	ambiguous	-0.384	Destabilizing	0.7	D	0.647	neutral	None	None	None	None	I
V/L	0.3395	likely_benign	0.3102	benign	-0.321	Destabilizing	0.094	N	0.598	neutral	N	0.509930083	None	None	I
V/M	0.2941	likely_benign	0.2564	benign	-0.563	Destabilizing	0.781	D	0.61	neutral	D	0.551204473	None	None	I
V/N	0.3999	ambiguous	0.3758	ambiguous	-0.168	Destabilizing	0.826	D	0.682	prob.neutral	None	None	None	None	I
V/P	0.8372	likely_pathogenic	0.8365	pathogenic	-0.297	Destabilizing	0.7	D	0.656	neutral	None	None	None	None	I
V/Q	0.4495	ambiguous	0.4393	ambiguous	-0.381	Destabilizing	0.826	D	0.658	neutral	None	None	None	None	I
V/R	0.4379	ambiguous	0.4414	ambiguous	0.062	Stabilizing	0.7	D	0.681	prob.neutral	None	None	None	None	I
V/S	0.3365	likely_benign	0.3368	benign	-0.472	Destabilizing	0.539	D	0.571	neutral	None	None	None	None	I
V/T	0.3383	likely_benign	0.3212	benign	-0.498	Destabilizing	0.25	N	0.571	neutral	None	None	None	None	I
V/W	0.8732	likely_pathogenic	0.8572	pathogenic	-0.778	Destabilizing	0.982	D	0.711	prob.delet.	None	None	None	None	I
V/Y	0.5786	likely_pathogenic	0.5633	ambiguous	-0.505	Destabilizing	0.826	D	0.623	neutral	None	None	None	None	I

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.