TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19587	58984;58985;58986	chr2:178593449;178593448;178593447	chr2:179458176;179458175;179458174
N2AB	17946	54061;54062;54063	chr2:178593449;178593448;178593447	chr2:179458176;179458175;179458174
N2A	17019	51280;51281;51282	chr2:178593449;178593448;178593447	chr2:179458176;179458175;179458174
N2B	10522	31789;31790;31791	chr2:178593449;178593448;178593447	chr2:179458176;179458175;179458174
Novex-1	10647	32164;32165;32166	chr2:178593449;178593448;178593447	chr2:179458176;179458175;179458174
Novex-2	10714	32365;32366;32367	chr2:178593449;178593448;178593447	chr2:179458176;179458175;179458174
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-30
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.38
• 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
I/V	rs916546048	None	None	N	0.159	0.053	0.163833314356	gnomAD-4.0.0	1.36952E-06	None	None	None	None	N	None	2.99383E-05	0	None	0	0	None	0	0	8.99666E-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
I/A	0.1203	likely_benign	0.1312	benign	-0.969	Destabilizing	0.016	N	0.401	neutral	None	None	None	None	N
I/C	0.4561	ambiguous	0.4722	ambiguous	-0.693	Destabilizing	0.676	D	0.597	neutral	None	None	None	None	N
I/D	0.3473	ambiguous	0.3675	ambiguous	-0.423	Destabilizing	0.072	N	0.637	neutral	None	None	None	None	N
I/E	0.2184	likely_benign	0.2362	benign	-0.496	Destabilizing	0.038	N	0.539	neutral	None	None	None	None	N
I/F	0.1257	likely_benign	0.1201	benign	-0.821	Destabilizing	0.171	N	0.59	neutral	N	0.453699391	None	None	N
I/G	0.3815	ambiguous	0.4189	ambiguous	-1.182	Destabilizing	0.072	N	0.549	neutral	None	None	None	None	N
I/H	0.2444	likely_benign	0.2516	benign	-0.459	Destabilizing	0.676	D	0.597	neutral	None	None	None	None	N
I/K	0.1601	likely_benign	0.1714	benign	-0.618	Destabilizing	None	N	0.483	neutral	None	None	None	None	N
I/L	0.0894	likely_benign	0.0896	benign	-0.513	Destabilizing	0.005	N	0.304	neutral	N	0.46133744	None	None	N
I/M	0.0787	likely_benign	0.0801	benign	-0.448	Destabilizing	0.171	N	0.561	neutral	N	0.494276578	None	None	N
I/N	0.1335	likely_benign	0.1413	benign	-0.386	Destabilizing	0.171	N	0.635	neutral	N	0.463876313	None	None	N
I/P	0.8635	likely_pathogenic	0.8548	pathogenic	-0.631	Destabilizing	0.356	N	0.631	neutral	None	None	None	None	N
I/Q	0.1796	likely_benign	0.1987	benign	-0.62	Destabilizing	0.12	N	0.623	neutral	None	None	None	None	N
I/R	0.1399	likely_benign	0.1387	benign	-0.029	Destabilizing	0.12	N	0.634	neutral	None	None	None	None	N
I/S	0.1257	likely_benign	0.131	benign	-0.879	Destabilizing	0.029	N	0.503	neutral	N	0.432993258	None	None	N
I/T	0.0753	likely_benign	0.0796	benign	-0.843	Destabilizing	None	N	0.271	neutral	N	0.372195516	None	None	N
I/V	0.0574	likely_benign	0.0581	benign	-0.631	Destabilizing	None	N	0.159	neutral	N	0.411447337	None	None	N
I/W	0.6476	likely_pathogenic	0.6331	pathogenic	-0.834	Destabilizing	0.864	D	0.634	neutral	None	None	None	None	N
I/Y	0.3853	ambiguous	0.3766	ambiguous	-0.602	Destabilizing	0.356	N	0.627	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.