TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2811	8656;8657;8658	chr2:178770270;178770269;178770268	chr2:179634997;179634996;179634995
N2AB	2811	8656;8657;8658	chr2:178770270;178770269;178770268	chr2:179634997;179634996;179634995
N2A	2811	8656;8657;8658	chr2:178770270;178770269;178770268	chr2:179634997;179634996;179634995
N2B	2765	8518;8519;8520	chr2:178770270;178770269;178770268	chr2:179634997;179634996;179634995
Novex-1	2765	8518;8519;8520	chr2:178770270;178770269;178770268	chr2:179634997;179634996;179634995
Novex-2	2765	8518;8519;8520	chr2:178770270;178770269;178770268	chr2:179634997;179634996;179634995
Novex-3	2811	8656;8657;8658	chr2:178770270;178770269;178770268	chr2:179634997;179634996;179634995

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-18
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.2625
• 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/A	rs1574566372	None	0.64	N	0.451	0.176	0.12205267543	gnomAD-4.0.0	1.59047E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85647E-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	0.0779	likely_benign	0.0828	benign	-0.511	Destabilizing	0.64	D	0.451	neutral	N	0.444736762	None	None	N
T/C	0.4516	ambiguous	0.5557	ambiguous	-0.258	Destabilizing	0.999	D	0.597	neutral	None	None	None	None	N
T/D	0.4288	ambiguous	0.5045	ambiguous	-0.078	Destabilizing	0.919	D	0.523	neutral	None	None	None	None	N
T/E	0.3685	ambiguous	0.4014	ambiguous	-0.117	Destabilizing	0.851	D	0.505	neutral	None	None	None	None	N
T/F	0.2994	likely_benign	0.383	ambiguous	-0.747	Destabilizing	0.976	D	0.674	neutral	None	None	None	None	N
T/G	0.2576	likely_benign	0.3437	ambiguous	-0.718	Destabilizing	0.851	D	0.569	neutral	None	None	None	None	N
T/H	0.3085	likely_benign	0.3856	ambiguous	-0.981	Destabilizing	0.997	D	0.663	neutral	None	None	None	None	N
T/I	0.1891	likely_benign	0.2207	benign	-0.069	Destabilizing	0.811	D	0.504	neutral	D	0.535603047	None	None	N
T/K	0.2836	likely_benign	0.3191	benign	-0.595	Destabilizing	0.851	D	0.515	neutral	None	None	None	None	N
T/L	0.1076	likely_benign	0.1386	benign	-0.069	Destabilizing	0.851	D	0.48	neutral	None	None	None	None	N
T/M	0.0833	likely_benign	0.0932	benign	0.124	Stabilizing	0.988	D	0.599	neutral	None	None	None	None	N
T/N	0.1313	likely_benign	0.1669	benign	-0.387	Destabilizing	0.968	D	0.471	neutral	N	0.450845952	None	None	N
T/P	0.1567	likely_benign	0.1871	benign	-0.185	Destabilizing	0.984	D	0.587	neutral	N	0.435403847	None	None	N
T/Q	0.2552	likely_benign	0.2956	benign	-0.574	Destabilizing	0.507	D	0.401	neutral	None	None	None	None	N
T/R	0.234	likely_benign	0.2556	benign	-0.306	Destabilizing	0.976	D	0.583	neutral	None	None	None	None	N
T/S	0.1022	likely_benign	0.127	benign	-0.602	Destabilizing	0.103	N	0.272	neutral	N	0.443230576	None	None	N
T/V	0.114	likely_benign	0.1347	benign	-0.185	Destabilizing	0.034	N	0.28	neutral	None	None	None	None	N
T/W	0.6655	likely_pathogenic	0.7284	pathogenic	-0.738	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
T/Y	0.386	ambiguous	0.456	ambiguous	-0.492	Destabilizing	0.988	D	0.675	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.