TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19194	57805;57806;57807	chr2:178595774;178595773;178595772	chr2:179460501;179460500;179460499
N2AB	17553	52882;52883;52884	chr2:178595774;178595773;178595772	chr2:179460501;179460500;179460499
N2A	16626	50101;50102;50103	chr2:178595774;178595773;178595772	chr2:179460501;179460500;179460499
N2B	10129	30610;30611;30612	chr2:178595774;178595773;178595772	chr2:179460501;179460500;179460499
Novex-1	10254	30985;30986;30987	chr2:178595774;178595773;178595772	chr2:179460501;179460500;179460499
Novex-2	10321	31186;31187;31188	chr2:178595774;178595773;178595772	chr2:179460501;179460500;179460499
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Fn3-27
• Domain position: 12
• Structural Position: 13
• Q(SASA): 0.6916
• 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
H/R	None	None	0.024	N	0.247	0.115	0.185906805712	gnomAD-4.0.0	6.86908E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.01502E-07	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
H/A	0.1219	likely_benign	0.1182	benign	-0.019	Destabilizing	0.014	N	0.217	neutral	None	None	None	None	N
H/C	0.1509	likely_benign	0.1609	benign	0.791	Stabilizing	0.864	D	0.264	neutral	None	None	None	None	N
H/D	0.0621	likely_benign	0.0669	benign	-0.059	Destabilizing	None	N	0.125	neutral	N	0.400499625	None	None	N
H/E	0.0949	likely_benign	0.0995	benign	0.001	Stabilizing	None	N	0.082	neutral	None	None	None	None	N
H/F	0.2415	likely_benign	0.2287	benign	0.893	Stabilizing	0.628	D	0.381	neutral	None	None	None	None	N
H/G	0.1449	likely_benign	0.1551	benign	-0.358	Destabilizing	0.031	N	0.243	neutral	None	None	None	None	N
H/I	0.1903	likely_benign	0.184	benign	0.881	Stabilizing	0.136	N	0.397	neutral	None	None	None	None	N
H/K	0.141	likely_benign	0.1487	benign	0.111	Stabilizing	0.016	N	0.251	neutral	None	None	None	None	N
H/L	0.1022	likely_benign	0.1002	benign	0.881	Stabilizing	0.055	N	0.364	neutral	N	0.388378476	None	None	N
H/M	0.2949	likely_benign	0.2732	benign	0.725	Stabilizing	0.628	D	0.279	neutral	None	None	None	None	N
H/N	0.0502	likely_benign	0.0494	benign	0.153	Stabilizing	0.012	N	0.238	neutral	N	0.421221614	None	None	N
H/P	0.2819	likely_benign	0.3839	ambiguous	0.606	Stabilizing	0.106	N	0.369	neutral	N	0.43547899	None	None	N
H/Q	0.0888	likely_benign	0.087	benign	0.323	Stabilizing	0.012	N	0.233	neutral	N	0.403713288	None	None	N
H/R	0.098	likely_benign	0.1002	benign	-0.553	Destabilizing	0.024	N	0.247	neutral	N	0.452851243	None	None	N
H/S	0.0878	likely_benign	0.0823	benign	0.234	Stabilizing	0.016	N	0.227	neutral	None	None	None	None	N
H/T	0.1065	likely_benign	0.1017	benign	0.395	Stabilizing	0.031	N	0.271	neutral	None	None	None	None	N
H/V	0.1297	likely_benign	0.128	benign	0.606	Stabilizing	0.136	N	0.363	neutral	None	None	None	None	N
H/W	0.3881	ambiguous	0.3984	ambiguous	0.996	Stabilizing	0.864	D	0.279	neutral	None	None	None	None	N
H/Y	0.0914	likely_benign	0.0896	benign	1.211	Stabilizing	0.266	N	0.321	neutral	N	0.454064751	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.