TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23398	70417;70418;70419	chr2:178575940;178575939;178575938	chr2:179440667;179440666;179440665
N2AB	21757	65494;65495;65496	chr2:178575940;178575939;178575938	chr2:179440667;179440666;179440665
N2A	20830	62713;62714;62715	chr2:178575940;178575939;178575938	chr2:179440667;179440666;179440665
N2B	14333	43222;43223;43224	chr2:178575940;178575939;178575938	chr2:179440667;179440666;179440665
Novex-1	14458	43597;43598;43599	chr2:178575940;178575939;178575938	chr2:179440667;179440666;179440665
Novex-2	14525	43798;43799;43800	chr2:178575940;178575939;178575938	chr2:179440667;179440666;179440665
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-129
• Domain position: 54
• Structural Position: 136
• Q(SASA): 0.1021
• 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
T/N	None	None	0.896	N	0.693	0.297	0.225215365344	gnomAD-4.0.0	6.84825E-07	None	None	None	None	N	None	2.99025E-05	0	None	0	0	None	0	0	0	0	0
T/S	rs1709923349	None	0.046	N	0.459	0.065	0.107399877778	gnomAD-4.0.0	1.36965E-06	None	None	None	None	N	None	5.9805E-05	0	None	0	0	None	0	0	0	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
T/A	0.4409	ambiguous	0.4538	ambiguous	-1.38	Destabilizing	0.64	D	0.619	neutral	N	0.492339845	None	None	N
T/C	0.802	likely_pathogenic	0.8051	pathogenic	-1.11	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
T/D	0.9887	likely_pathogenic	0.9912	pathogenic	-2.453	Highly Destabilizing	0.919	D	0.721	prob.delet.	None	None	None	None	N
T/E	0.9936	likely_pathogenic	0.9949	pathogenic	-2.116	Highly Destabilizing	0.919	D	0.719	prob.delet.	None	None	None	None	N
T/F	0.9868	likely_pathogenic	0.9896	pathogenic	-0.769	Destabilizing	0.996	D	0.753	deleterious	None	None	None	None	N
T/G	0.8405	likely_pathogenic	0.853	pathogenic	-1.83	Destabilizing	0.851	D	0.715	prob.delet.	None	None	None	None	N
T/H	0.9623	likely_pathogenic	0.968	pathogenic	-1.617	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
T/I	0.9592	likely_pathogenic	0.9673	pathogenic	-0.12	Destabilizing	0.984	D	0.743	deleterious	N	0.476745657	None	None	N
T/K	0.9945	likely_pathogenic	0.9957	pathogenic	-0.464	Destabilizing	0.919	D	0.72	prob.delet.	None	None	None	None	N
T/L	0.8502	likely_pathogenic	0.8649	pathogenic	-0.12	Destabilizing	0.919	D	0.706	prob.neutral	None	None	None	None	N
T/M	0.7145	likely_pathogenic	0.7486	pathogenic	-0.659	Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
T/N	0.8644	likely_pathogenic	0.8848	pathogenic	-1.656	Destabilizing	0.896	D	0.693	prob.neutral	N	0.5143527	None	None	N
T/P	0.9753	likely_pathogenic	0.981	pathogenic	-0.518	Destabilizing	0.984	D	0.742	deleterious	N	0.48911592	None	None	N
T/Q	0.975	likely_pathogenic	0.9782	pathogenic	-1.075	Destabilizing	0.988	D	0.755	deleterious	None	None	None	None	N
T/R	0.9907	likely_pathogenic	0.9924	pathogenic	-1.047	Destabilizing	0.976	D	0.737	prob.delet.	None	None	None	None	N
T/S	0.2059	likely_benign	0.2179	benign	-1.819	Destabilizing	0.046	N	0.459	neutral	N	0.460843502	None	None	N
T/V	0.8354	likely_pathogenic	0.8498	pathogenic	-0.518	Destabilizing	0.919	D	0.675	prob.neutral	None	None	None	None	N
T/W	0.9973	likely_pathogenic	0.9978	pathogenic	-1.098	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
T/Y	0.9877	likely_pathogenic	0.9899	pathogenic	-0.718	Destabilizing	0.996	D	0.765	deleterious	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.