TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23453	70582;70583;70584	chr2:178575775;178575774;178575773	chr2:179440502;179440501;179440500
N2AB	21812	65659;65660;65661	chr2:178575775;178575774;178575773	chr2:179440502;179440501;179440500
N2A	20885	62878;62879;62880	chr2:178575775;178575774;178575773	chr2:179440502;179440501;179440500
N2B	14388	43387;43388;43389	chr2:178575775;178575774;178575773	chr2:179440502;179440501;179440500
Novex-1	14513	43762;43763;43764	chr2:178575775;178575774;178575773	chr2:179440502;179440501;179440500
Novex-2	14580	43963;43964;43965	chr2:178575775;178575774;178575773	chr2:179440502;179440501;179440500
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-58
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.1724
• 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/I	rs1435352674	0.074	0.012	N	0.385	0.176	0.255777322467	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.58E-05	None	0	None	0	0	0
T/I	rs1435352674	0.074	0.012	N	0.385	0.176	0.255777322467	gnomAD-4.0.0	1.59201E-06	None	None	None	None	N	None	0	0	None	0	2.77654E-05	None	0	0	0	0	0
T/N	None	None	0.947	N	0.616	0.34	0.321393169273	gnomAD-4.0.0	3.18402E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72037E-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	0.1311	likely_benign	0.1409	benign	-0.75	Destabilizing	0.212	N	0.502	neutral	N	0.475460616	None	None	N
T/C	0.3627	ambiguous	0.4019	ambiguous	-0.802	Destabilizing	0.997	D	0.688	prob.neutral	None	None	None	None	N
T/D	0.6754	likely_pathogenic	0.7324	pathogenic	-1.795	Destabilizing	0.886	D	0.65	neutral	None	None	None	None	N
T/E	0.5451	ambiguous	0.6209	pathogenic	-1.68	Destabilizing	0.963	D	0.643	neutral	None	None	None	None	N
T/F	0.2111	likely_benign	0.2407	benign	-0.575	Destabilizing	0.98	D	0.705	prob.neutral	None	None	None	None	N
T/G	0.4352	ambiguous	0.4654	ambiguous	-1.096	Destabilizing	0.985	D	0.651	neutral	None	None	None	None	N
T/H	0.3109	likely_benign	0.3395	benign	-1.449	Destabilizing	0.998	D	0.72	prob.delet.	None	None	None	None	N
T/I	0.1235	likely_benign	0.1263	benign	0.115	Stabilizing	0.012	N	0.385	neutral	N	0.518001586	None	None	N
T/K	0.394	ambiguous	0.4678	ambiguous	-0.849	Destabilizing	0.973	D	0.646	neutral	None	None	None	None	N
T/L	0.0967	likely_benign	0.0989	benign	0.115	Stabilizing	0.266	N	0.478	neutral	None	None	None	None	N
T/M	0.0802	likely_benign	0.0801	benign	0.233	Stabilizing	0.985	D	0.689	prob.neutral	None	None	None	None	N
T/N	0.1874	likely_benign	0.207	benign	-1.372	Destabilizing	0.947	D	0.616	neutral	N	0.475055769	None	None	N
T/P	0.7578	likely_pathogenic	0.8003	pathogenic	-0.141	Destabilizing	0.947	D	0.67	neutral	N	0.519519939	None	None	N
T/Q	0.3318	likely_benign	0.3617	ambiguous	-1.338	Destabilizing	0.981	D	0.705	prob.neutral	None	None	None	None	N
T/R	0.3344	likely_benign	0.4129	ambiguous	-0.849	Destabilizing	0.99	D	0.698	prob.neutral	None	None	None	None	N
T/S	0.1426	likely_benign	0.1563	benign	-1.409	Destabilizing	0.352	N	0.506	neutral	N	0.46741805	None	None	N
T/V	0.1076	likely_benign	0.108	benign	-0.141	Destabilizing	0.206	N	0.47	neutral	None	None	None	None	N
T/W	0.5948	likely_pathogenic	0.6224	pathogenic	-0.776	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
T/Y	0.2776	likely_benign	0.3037	benign	-0.399	Destabilizing	0.99	D	0.733	prob.delet.	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.