TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18438	55537;55538;55539	chr2:178601778;178601777;178601776	chr2:179466505;179466504;179466503
N2AB	16797	50614;50615;50616	chr2:178601778;178601777;178601776	chr2:179466505;179466504;179466503
N2A	15870	47833;47834;47835	chr2:178601778;178601777;178601776	chr2:179466505;179466504;179466503
N2B	9373	28342;28343;28344	chr2:178601778;178601777;178601776	chr2:179466505;179466504;179466503
Novex-1	9498	28717;28718;28719	chr2:178601778;178601777;178601776	chr2:179466505;179466504;179466503
Novex-2	9565	28918;28919;28920	chr2:178601778;178601777;178601776	chr2:179466505;179466504;179466503
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-115
• Domain position: 57
• Structural Position: 130
• Q(SASA): 0.2174
• 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
A/T	rs1416049620	None	0.007	N	0.142	0.135	0.195762928549	gnomAD-4.0.0	1.62326E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.50267E-05	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
A/C	0.3351	likely_benign	0.4132	ambiguous	-0.689	Destabilizing	0.998	D	0.465	neutral	None	None	None	None	N
A/D	0.1649	likely_benign	0.235	benign	-0.29	Destabilizing	0.801	D	0.385	neutral	N	0.448035361	None	None	N
A/E	0.173	likely_benign	0.2313	benign	-0.45	Destabilizing	0.842	D	0.398	neutral	None	None	None	None	N
A/F	0.2441	likely_benign	0.328	benign	-0.818	Destabilizing	0.974	D	0.476	neutral	None	None	None	None	N
A/G	0.0969	likely_benign	0.1161	benign	-0.11	Destabilizing	0.625	D	0.415	neutral	N	0.433068695	None	None	N
A/H	0.2854	likely_benign	0.3786	ambiguous	-0.185	Destabilizing	0.998	D	0.472	neutral	None	None	None	None	N
A/I	0.1856	likely_benign	0.2411	benign	-0.264	Destabilizing	0.842	D	0.376	neutral	None	None	None	None	N
A/K	0.2104	likely_benign	0.3252	benign	-0.367	Destabilizing	0.842	D	0.397	neutral	None	None	None	None	N
A/L	0.1231	likely_benign	0.158	benign	-0.264	Destabilizing	0.525	D	0.385	neutral	None	None	None	None	N
A/M	0.1529	likely_benign	0.185	benign	-0.315	Destabilizing	0.991	D	0.453	neutral	None	None	None	None	N
A/N	0.1308	likely_benign	0.1782	benign	-0.078	Destabilizing	0.949	D	0.417	neutral	None	None	None	None	N
A/P	0.3725	ambiguous	0.566	pathogenic	-0.18	Destabilizing	0.966	D	0.387	neutral	N	0.4834388	None	None	N
A/Q	0.2081	likely_benign	0.2738	benign	-0.352	Destabilizing	0.974	D	0.435	neutral	None	None	None	None	N
A/R	0.2106	likely_benign	0.3134	benign	0.036	Stabilizing	0.949	D	0.398	neutral	None	None	None	None	N
A/S	0.0681	likely_benign	0.0759	benign	-0.27	Destabilizing	0.454	N	0.417	neutral	N	0.393086155	None	None	N
A/T	0.0646	likely_benign	0.0709	benign	-0.353	Destabilizing	0.007	N	0.142	neutral	N	0.367323706	None	None	N
A/V	0.1023	likely_benign	0.1242	benign	-0.18	Destabilizing	0.454	N	0.421	neutral	N	0.442341539	None	None	N
A/W	0.5609	ambiguous	0.6902	pathogenic	-0.945	Destabilizing	0.998	D	0.53	neutral	None	None	None	None	N
A/Y	0.3529	ambiguous	0.4503	ambiguous	-0.587	Destabilizing	0.991	D	0.47	neutral	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.