TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1529	4810;4811;4812	chr2:178777480;178777479;178777478	chr2:179642207;179642206;179642205
N2AB	1529	4810;4811;4812	chr2:178777480;178777479;178777478	chr2:179642207;179642206;179642205
N2A	1529	4810;4811;4812	chr2:178777480;178777479;178777478	chr2:179642207;179642206;179642205
N2B	1483	4672;4673;4674	chr2:178777480;178777479;178777478	chr2:179642207;179642206;179642205
Novex-1	1483	4672;4673;4674	chr2:178777480;178777479;178777478	chr2:179642207;179642206;179642205
Novex-2	1483	4672;4673;4674	chr2:178777480;178777479;178777478	chr2:179642207;179642206;179642205
Novex-3	1529	4810;4811;4812	chr2:178777480;178777479;178777478	chr2:179642207;179642206;179642205

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-6
• Domain position: 73
• Structural Position: 155
• Q(SASA): 0.2623
• 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
T/I	None	None	0.009	D	0.38	0.411	0.497021753114	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
T/S	None	None	0.379	N	0.482	0.237	0.289098819767	gnomAD-4.0.0	1.36832E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99344E-07	0	1.65623E-05

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	0.1271	likely_benign	0.1396	benign	-1.438	Destabilizing	0.002	N	0.183	neutral	D	0.571672247	None	None	I
T/C	0.5491	ambiguous	0.5941	pathogenic	-0.815	Destabilizing	0.977	D	0.541	neutral	None	None	None	None	I
T/D	0.6327	likely_pathogenic	0.6692	pathogenic	-0.941	Destabilizing	0.92	D	0.515	neutral	None	None	None	None	I
T/E	0.4023	ambiguous	0.4299	ambiguous	-0.728	Destabilizing	0.85	D	0.507	neutral	None	None	None	None	I
T/F	0.421	ambiguous	0.4418	ambiguous	-1.19	Destabilizing	0.85	D	0.62	neutral	None	None	None	None	I
T/G	0.4732	ambiguous	0.521	ambiguous	-1.828	Destabilizing	0.447	N	0.523	neutral	None	None	None	None	I
T/H	0.3073	likely_benign	0.3262	benign	-1.719	Destabilizing	0.992	D	0.629	neutral	None	None	None	None	I
T/I	0.2259	likely_benign	0.246	benign	-0.402	Destabilizing	0.009	N	0.38	neutral	D	0.597221595	None	None	I
T/K	0.2335	likely_benign	0.2497	benign	-0.062	Destabilizing	0.85	D	0.506	neutral	None	None	None	None	I
T/L	0.1548	likely_benign	0.1697	benign	-0.402	Destabilizing	0.103	N	0.473	neutral	None	None	None	None	I
T/M	0.0906	likely_benign	0.0944	benign	-0.483	Destabilizing	0.85	D	0.555	neutral	None	None	None	None	I
T/N	0.1802	likely_benign	0.1959	benign	-0.659	Destabilizing	0.896	D	0.479	neutral	D	0.676499294	None	None	I
T/P	0.9297	likely_pathogenic	0.9447	pathogenic	-0.721	Destabilizing	0.896	D	0.545	neutral	D	0.764493422	None	None	I
T/Q	0.2361	likely_benign	0.254	benign	-0.481	Destabilizing	0.92	D	0.558	neutral	None	None	None	None	I
T/R	0.1967	likely_benign	0.209	benign	-0.319	Destabilizing	0.85	D	0.545	neutral	None	None	None	None	I
T/S	0.1606	likely_benign	0.1728	benign	-1.049	Destabilizing	0.379	N	0.482	neutral	N	0.510147617	None	None	I
T/V	0.1733	likely_benign	0.1907	benign	-0.721	Destabilizing	0.005	N	0.278	neutral	None	None	None	None	I
T/W	0.7663	likely_pathogenic	0.7822	pathogenic	-1.169	Destabilizing	0.992	D	0.684	prob.neutral	None	None	None	None	I
T/Y	0.4743	ambiguous	0.4868	ambiguous	-0.827	Destabilizing	0.92	D	0.64	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.