TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23427	70504;70505;70506	chr2:178575853;178575852;178575851	chr2:179440580;179440579;179440578
N2AB	21786	65581;65582;65583	chr2:178575853;178575852;178575851	chr2:179440580;179440579;179440578
N2A	20859	62800;62801;62802	chr2:178575853;178575852;178575851	chr2:179440580;179440579;179440578
N2B	14362	43309;43310;43311	chr2:178575853;178575852;178575851	chr2:179440580;179440579;179440578
Novex-1	14487	43684;43685;43686	chr2:178575853;178575852;178575851	chr2:179440580;179440579;179440578
Novex-2	14554	43885;43886;43887	chr2:178575853;178575852;178575851	chr2:179440580;179440579;179440578
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-129
• Domain position: 83
• Structural Position: 171
• Q(SASA): 0.6379
• 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
F/S	None	None	0.204	N	0.55	0.382	0.681492719615	gnomAD-4.0.0	1.5917E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85936E-06	0	0
F/Y	rs779382645	0.043	0.981	N	0.576	0.254	0.571380689955	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.88E-06	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
F/A	0.7048	likely_pathogenic	0.7284	pathogenic	-1.421	Destabilizing	0.845	D	0.651	neutral	None	None	None	None	I
F/C	0.6009	likely_pathogenic	0.591	pathogenic	-0.646	Destabilizing	0.999	D	0.75	deleterious	N	0.488490713	None	None	I
F/D	0.9294	likely_pathogenic	0.9284	pathogenic	0.347	Stabilizing	0.975	D	0.738	prob.delet.	None	None	None	None	I
F/E	0.9461	likely_pathogenic	0.9437	pathogenic	0.365	Stabilizing	0.975	D	0.731	prob.delet.	None	None	None	None	I
F/G	0.9025	likely_pathogenic	0.9046	pathogenic	-1.67	Destabilizing	0.845	D	0.69	prob.neutral	None	None	None	None	I
F/H	0.72	likely_pathogenic	0.7244	pathogenic	-0.027	Destabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	I
F/I	0.4486	ambiguous	0.447	ambiguous	-0.734	Destabilizing	0.983	D	0.645	neutral	N	0.516529867	None	None	I
F/K	0.9561	likely_pathogenic	0.9557	pathogenic	-0.548	Destabilizing	0.975	D	0.737	prob.delet.	None	None	None	None	I
F/L	0.9558	likely_pathogenic	0.9548	pathogenic	-0.734	Destabilizing	0.892	D	0.6	neutral	N	0.502965924	None	None	I
F/M	0.6417	likely_pathogenic	0.6549	pathogenic	-0.628	Destabilizing	0.996	D	0.659	neutral	None	None	None	None	I
F/N	0.6893	likely_pathogenic	0.7003	pathogenic	-0.526	Destabilizing	0.975	D	0.749	deleterious	None	None	None	None	I
F/P	0.9945	likely_pathogenic	0.9912	pathogenic	-0.947	Destabilizing	0.987	D	0.759	deleterious	None	None	None	None	I
F/Q	0.8998	likely_pathogenic	0.8964	pathogenic	-0.58	Destabilizing	0.975	D	0.759	deleterious	None	None	None	None	I
F/R	0.9276	likely_pathogenic	0.9257	pathogenic	0.012	Stabilizing	0.975	D	0.754	deleterious	None	None	None	None	I
F/S	0.4919	ambiguous	0.5332	ambiguous	-1.274	Destabilizing	0.204	N	0.55	neutral	N	0.427908018	None	None	I
F/T	0.4857	ambiguous	0.5318	ambiguous	-1.164	Destabilizing	0.845	D	0.681	prob.neutral	None	None	None	None	I
F/V	0.4125	ambiguous	0.4236	ambiguous	-0.947	Destabilizing	0.892	D	0.686	prob.neutral	N	0.471546939	None	None	I
F/W	0.6983	likely_pathogenic	0.699	pathogenic	-0.199	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	I
F/Y	0.2496	likely_benign	0.2481	benign	-0.324	Destabilizing	0.981	D	0.576	neutral	N	0.494154439	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.