TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22323	67192;67193;67194	chr2:178580412;178580411;178580410	chr2:179445139;179445138;179445137
N2AB	20682	62269;62270;62271	chr2:178580412;178580411;178580410	chr2:179445139;179445138;179445137
N2A	19755	59488;59489;59490	chr2:178580412;178580411;178580410	chr2:179445139;179445138;179445137
N2B	13258	39997;39998;39999	chr2:178580412;178580411;178580410	chr2:179445139;179445138;179445137
Novex-1	13383	40372;40373;40374	chr2:178580412;178580411;178580410	chr2:179445139;179445138;179445137
Novex-2	13450	40573;40574;40575	chr2:178580412;178580411;178580410	chr2:179445139;179445138;179445137
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-126
• Domain position: 59
• Structural Position: 143
• Q(SASA): 0.6698
• 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
N/I	None	None	None	N	0.335	0.302	0.414930877219	gnomAD-4.0.0	1.20036E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31254E-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
N/A	0.2969	likely_benign	0.3538	ambiguous	-0.438	Destabilizing	0.016	N	0.36	neutral	None	None	None	None	I
N/C	0.4363	ambiguous	0.4817	ambiguous	0.419	Stabilizing	0.864	D	0.415	neutral	None	None	None	None	I
N/D	0.1609	likely_benign	0.1802	benign	-0.362	Destabilizing	None	N	0.121	neutral	N	0.460750289	None	None	I
N/E	0.3794	ambiguous	0.4592	ambiguous	-0.395	Destabilizing	0.001	N	0.148	neutral	None	None	None	None	I
N/F	0.6188	likely_pathogenic	0.6711	pathogenic	-0.82	Destabilizing	0.214	N	0.434	neutral	None	None	None	None	I
N/G	0.3588	ambiguous	0.4022	ambiguous	-0.616	Destabilizing	0.031	N	0.277	neutral	None	None	None	None	I
N/H	0.1638	likely_benign	0.173	benign	-0.727	Destabilizing	0.295	N	0.355	neutral	N	0.469636221	None	None	I
N/I	0.3771	ambiguous	0.4264	ambiguous	-0.05	Destabilizing	None	N	0.335	neutral	N	0.485627336	None	None	I
N/K	0.2734	likely_benign	0.3865	ambiguous	0.124	Stabilizing	None	N	0.195	neutral	N	0.448783856	None	None	I
N/L	0.3563	ambiguous	0.4269	ambiguous	-0.05	Destabilizing	0.013	N	0.417	neutral	None	None	None	None	I
N/M	0.3581	ambiguous	0.4151	ambiguous	0.608	Stabilizing	0.214	N	0.398	neutral	None	None	None	None	I
N/P	0.8482	likely_pathogenic	0.8873	pathogenic	-0.154	Destabilizing	0.356	N	0.414	neutral	None	None	None	None	I
N/Q	0.3421	ambiguous	0.4046	ambiguous	-0.48	Destabilizing	0.038	N	0.333	neutral	None	None	None	None	I
N/R	0.3841	ambiguous	0.4893	ambiguous	0.27	Stabilizing	0.038	N	0.31	neutral	None	None	None	None	I
N/S	0.1458	likely_benign	0.1564	benign	-0.133	Destabilizing	0.012	N	0.307	neutral	N	0.503829062	None	None	I
N/T	0.1872	likely_benign	0.2249	benign	-0.03	Destabilizing	0.055	N	0.246	neutral	N	0.459925757	None	None	I
N/V	0.3539	ambiguous	0.4042	ambiguous	-0.154	Destabilizing	0.013	N	0.418	neutral	None	None	None	None	I
N/W	0.8321	likely_pathogenic	0.8589	pathogenic	-0.745	Destabilizing	0.864	D	0.525	neutral	None	None	None	None	I
N/Y	0.1871	likely_benign	0.2203	benign	-0.478	Destabilizing	0.295	N	0.405	neutral	N	0.478536991	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.