TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21674	65245;65246;65247	chr2:178584531;178584530;178584529	chr2:179449258;179449257;179449256
N2AB	20033	60322;60323;60324	chr2:178584531;178584530;178584529	chr2:179449258;179449257;179449256
N2A	19106	57541;57542;57543	chr2:178584531;178584530;178584529	chr2:179449258;179449257;179449256
N2B	12609	38050;38051;38052	chr2:178584531;178584530;178584529	chr2:179449258;179449257;179449256
Novex-1	12734	38425;38426;38427	chr2:178584531;178584530;178584529	chr2:179449258;179449257;179449256
Novex-2	12801	38626;38627;38628	chr2:178584531;178584530;178584529	chr2:179449258;179449257;179449256
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-45
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.4135
• 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
D/Y	None	None	0.999	N	0.661	0.451	0.518312163451	gnomAD-4.0.0	2.73811E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59901E-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
D/A	0.4682	ambiguous	0.4249	ambiguous	-0.204	Destabilizing	0.956	D	0.465	neutral	N	0.482359923	None	None	N
D/C	0.8802	likely_pathogenic	0.8502	pathogenic	0.178	Stabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
D/E	0.2333	likely_benign	0.2371	benign	-0.683	Destabilizing	0.37	N	0.159	neutral	N	0.469823637	None	None	N
D/F	0.8344	likely_pathogenic	0.8242	pathogenic	-0.507	Destabilizing	0.998	D	0.66	neutral	None	None	None	None	N
D/G	0.3758	ambiguous	0.3439	ambiguous	-0.44	Destabilizing	0.989	D	0.477	neutral	N	0.473788321	None	None	N
D/H	0.6056	likely_pathogenic	0.5369	ambiguous	-0.816	Destabilizing	1.0	D	0.513	neutral	D	0.522868688	None	None	N
D/I	0.7762	likely_pathogenic	0.7716	pathogenic	0.376	Stabilizing	0.99	D	0.619	neutral	None	None	None	None	N
D/K	0.7809	likely_pathogenic	0.755	pathogenic	0.079	Stabilizing	0.983	D	0.457	neutral	None	None	None	None	N
D/L	0.7414	likely_pathogenic	0.719	pathogenic	0.376	Stabilizing	0.99	D	0.561	neutral	None	None	None	None	N
D/M	0.8639	likely_pathogenic	0.8571	pathogenic	0.787	Stabilizing	0.999	D	0.641	neutral	None	None	None	None	N
D/N	0.1686	likely_benign	0.1585	benign	-0.112	Destabilizing	0.997	D	0.478	neutral	N	0.473130514	None	None	N
D/P	0.9768	likely_pathogenic	0.9683	pathogenic	0.207	Stabilizing	0.999	D	0.525	neutral	None	None	None	None	N
D/Q	0.6462	likely_pathogenic	0.6054	pathogenic	-0.092	Destabilizing	0.995	D	0.493	neutral	None	None	None	None	N
D/R	0.8005	likely_pathogenic	0.7613	pathogenic	0.009	Stabilizing	0.995	D	0.618	neutral	None	None	None	None	N
D/S	0.2916	likely_benign	0.2738	benign	-0.259	Destabilizing	0.983	D	0.451	neutral	None	None	None	None	N
D/T	0.4805	ambiguous	0.463	ambiguous	-0.081	Destabilizing	0.995	D	0.447	neutral	None	None	None	None	N
D/V	0.5755	likely_pathogenic	0.561	ambiguous	0.207	Stabilizing	0.576	D	0.4	neutral	N	0.516682329	None	None	N
D/W	0.9583	likely_pathogenic	0.9442	pathogenic	-0.535	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	N
D/Y	0.4203	ambiguous	0.3871	ambiguous	-0.305	Destabilizing	0.999	D	0.661	neutral	N	0.490095377	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.