TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2522	7789;7790;7791	chr2:178773492;178773491;178773490	chr2:179638219;179638218;179638217
N2AB	2522	7789;7790;7791	chr2:178773492;178773491;178773490	chr2:179638219;179638218;179638217
N2A	2522	7789;7790;7791	chr2:178773492;178773491;178773490	chr2:179638219;179638218;179638217
N2B	2476	7651;7652;7653	chr2:178773492;178773491;178773490	chr2:179638219;179638218;179638217
Novex-1	2476	7651;7652;7653	chr2:178773492;178773491;178773490	chr2:179638219;179638218;179638217
Novex-2	2476	7651;7652;7653	chr2:178773492;178773491;178773490	chr2:179638219;179638218;179638217
Novex-3	2522	7789;7790;7791	chr2:178773492;178773491;178773490	chr2:179638219;179638218;179638217

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-14
• Domain position: 78
• Structural Position: 166
• Q(SASA): 0.2346
• 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
V/A	rs1163155086	None	0.489	N	0.545	0.191	0.258779203287	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	6.07533E-05	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	0.1101	likely_benign	0.1065	benign	-0.946	Destabilizing	0.489	N	0.545	neutral	N	0.438221487	None	None	N
V/C	0.6665	likely_pathogenic	0.6491	pathogenic	-0.742	Destabilizing	0.998	D	0.615	neutral	None	None	None	None	N
V/D	0.3826	ambiguous	0.3712	ambiguous	-0.692	Destabilizing	0.942	D	0.683	prob.neutral	N	0.446996539	None	None	N
V/E	0.271	likely_benign	0.2718	benign	-0.739	Destabilizing	0.956	D	0.59	neutral	None	None	None	None	N
V/F	0.2085	likely_benign	0.1998	benign	-0.773	Destabilizing	0.942	D	0.631	neutral	N	0.475171803	None	None	N
V/G	0.209	likely_benign	0.2027	benign	-1.191	Destabilizing	0.698	D	0.646	neutral	N	0.447853438	None	None	N
V/H	0.4956	ambiguous	0.4831	ambiguous	-0.746	Destabilizing	0.998	D	0.695	prob.neutral	None	None	None	None	N
V/I	0.0912	likely_benign	0.0888	benign	-0.409	Destabilizing	0.489	N	0.571	neutral	N	0.448157154	None	None	N
V/K	0.2632	likely_benign	0.2633	benign	-0.937	Destabilizing	0.956	D	0.591	neutral	None	None	None	None	N
V/L	0.2521	likely_benign	0.2438	benign	-0.409	Destabilizing	0.489	N	0.526	neutral	N	0.437151705	None	None	N
V/M	0.1446	likely_benign	0.1402	benign	-0.402	Destabilizing	0.559	D	0.482	neutral	None	None	None	None	N
V/N	0.253	likely_benign	0.2518	benign	-0.691	Destabilizing	0.956	D	0.698	prob.neutral	None	None	None	None	N
V/P	0.8981	likely_pathogenic	0.8804	pathogenic	-0.551	Destabilizing	0.978	D	0.667	neutral	None	None	None	None	N
V/Q	0.2737	likely_benign	0.2688	benign	-0.871	Destabilizing	0.956	D	0.669	neutral	None	None	None	None	N
V/R	0.2557	likely_benign	0.2569	benign	-0.425	Destabilizing	0.956	D	0.703	prob.neutral	None	None	None	None	N
V/S	0.1535	likely_benign	0.1545	benign	-1.124	Destabilizing	0.16	N	0.434	neutral	None	None	None	None	N
V/T	0.112	likely_benign	0.1103	benign	-1.066	Destabilizing	0.754	D	0.532	neutral	None	None	None	None	N
V/W	0.8213	likely_pathogenic	0.7949	pathogenic	-0.926	Destabilizing	0.998	D	0.719	prob.delet.	None	None	None	None	N
V/Y	0.5376	ambiguous	0.5234	ambiguous	-0.639	Destabilizing	0.993	D	0.629	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.