TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2426	7501;7502;7503	chr2:178773892;178773891;178773890	chr2:179638619;179638618;179638617
N2AB	2426	7501;7502;7503	chr2:178773892;178773891;178773890	chr2:179638619;179638618;179638617
N2A	2426	7501;7502;7503	chr2:178773892;178773891;178773890	chr2:179638619;179638618;179638617
N2B	2380	7363;7364;7365	chr2:178773892;178773891;178773890	chr2:179638619;179638618;179638617
Novex-1	2380	7363;7364;7365	chr2:178773892;178773891;178773890	chr2:179638619;179638618;179638617
Novex-2	2380	7363;7364;7365	chr2:178773892;178773891;178773890	chr2:179638619;179638618;179638617
Novex-3	2426	7501;7502;7503	chr2:178773892;178773891;178773890	chr2:179638619;179638618;179638617

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-13
• Domain position: 71
• Structural Position: 155
• Q(SASA): 0.1408
• 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
S/C	None	None	1.0	D	0.819	0.642	0.811379597274	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
S/A	0.0992	likely_benign	0.0958	benign	-1.14	Destabilizing	0.997	D	0.488	neutral	D	0.584443812	None	None	N
S/C	0.1099	likely_benign	0.1078	benign	-1.054	Destabilizing	1.0	D	0.819	deleterious	D	0.693857774	None	None	N
S/D	0.562	ambiguous	0.5363	ambiguous	-1.218	Destabilizing	0.999	D	0.559	neutral	None	None	None	None	N
S/E	0.623	likely_pathogenic	0.6072	pathogenic	-1.057	Destabilizing	0.999	D	0.547	neutral	None	None	None	None	N
S/F	0.2186	likely_benign	0.2074	benign	-1.358	Destabilizing	1.0	D	0.864	deleterious	D	0.695335063	None	None	N
S/G	0.1523	likely_benign	0.1432	benign	-1.469	Destabilizing	0.999	D	0.539	neutral	None	None	None	None	N
S/H	0.3474	ambiguous	0.3326	benign	-1.769	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
S/I	0.1846	likely_benign	0.1734	benign	-0.312	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
S/K	0.7451	likely_pathogenic	0.7161	pathogenic	-0.179	Destabilizing	0.999	D	0.557	neutral	None	None	None	None	N
S/L	0.1163	likely_benign	0.1118	benign	-0.312	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
S/M	0.2213	likely_benign	0.2106	benign	-0.265	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
S/N	0.2031	likely_benign	0.1908	benign	-0.801	Destabilizing	0.999	D	0.561	neutral	None	None	None	None	N
S/P	0.9799	likely_pathogenic	0.9808	pathogenic	-0.558	Destabilizing	1.0	D	0.803	deleterious	D	0.693857774	None	None	N
S/Q	0.5383	ambiguous	0.5173	ambiguous	-0.714	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
S/R	0.6079	likely_pathogenic	0.5722	pathogenic	-0.417	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
S/T	0.0753	likely_benign	0.0738	benign	-0.64	Destabilizing	0.999	D	0.503	neutral	N	0.517717318	None	None	N
S/V	0.1837	likely_benign	0.1729	benign	-0.558	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
S/W	0.4667	ambiguous	0.45	ambiguous	-1.413	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
S/Y	0.2165	likely_benign	0.2104	benign	-1.024	Destabilizing	1.0	D	0.867	deleterious	D	0.635839721	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.