TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16133	48622;48623;48624	chr2:178615704;178615703;178615702	chr2:179480431;179480430;179480429
N2AB	14492	43699;43700;43701	chr2:178615704;178615703;178615702	chr2:179480431;179480430;179480429
N2A	13565	40918;40919;40920	chr2:178615704;178615703;178615702	chr2:179480431;179480430;179480429
N2B	7068	21427;21428;21429	chr2:178615704;178615703;178615702	chr2:179480431;179480430;179480429
Novex-1	7193	21802;21803;21804	chr2:178615704;178615703;178615702	chr2:179480431;179480430;179480429
Novex-2	7260	22003;22004;22005	chr2:178615704;178615703;178615702	chr2:179480431;179480430;179480429
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-4
• Domain position: 79
• Structural Position: 112
• Q(SASA): 0.0884
• 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
N/K	rs1060500470	None	1.0	D	0.763	0.67	0.257292322809	Rees (2021)	None	MmD	comp het with R5308*	None	None	N	Genetic analysis of TTN in 30 CM patients; comp het with truncating; Domain unfolded in vitro	None	None	None	None	None	None	None	None	None	None	None

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	0.998	likely_pathogenic	0.9975	pathogenic	0.331	Stabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
N/C	0.9805	likely_pathogenic	0.9779	pathogenic	-0.138	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
N/D	0.99	likely_pathogenic	0.9891	pathogenic	-2.32	Highly Destabilizing	0.999	D	0.609	neutral	D	0.667459104	None	None	N
N/E	0.9984	likely_pathogenic	0.9978	pathogenic	-2.167	Highly Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
N/F	0.9996	likely_pathogenic	0.9995	pathogenic	0.06	Stabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
N/G	0.9898	likely_pathogenic	0.9889	pathogenic	0.073	Stabilizing	0.999	D	0.579	neutral	None	None	None	None	N
N/H	0.9872	likely_pathogenic	0.9864	pathogenic	0.005	Stabilizing	1.0	D	0.778	deleterious	D	0.74558539	None	None	N
N/I	0.9974	likely_pathogenic	0.9958	pathogenic	0.944	Stabilizing	1.0	D	0.859	deleterious	D	0.765642963	None	None	N
N/K	0.9986	likely_pathogenic	0.9979	pathogenic	0.323	Stabilizing	1.0	D	0.763	deleterious	D	0.795822554	None	None	N
N/L	0.9917	likely_pathogenic	0.9885	pathogenic	0.944	Stabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
N/M	0.9968	likely_pathogenic	0.9952	pathogenic	0.935	Stabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
N/P	0.9986	likely_pathogenic	0.998	pathogenic	0.769	Stabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
N/Q	0.9983	likely_pathogenic	0.9979	pathogenic	-0.654	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
N/R	0.9978	likely_pathogenic	0.997	pathogenic	0.222	Stabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
N/S	0.897	likely_pathogenic	0.8952	pathogenic	-0.406	Destabilizing	0.999	D	0.593	neutral	D	0.643071474	None	None	N
N/T	0.9776	likely_pathogenic	0.9707	pathogenic	-0.133	Destabilizing	0.999	D	0.728	prob.delet.	D	0.610046809	None	None	N
N/V	0.9967	likely_pathogenic	0.995	pathogenic	0.769	Stabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
N/W	0.9998	likely_pathogenic	0.9997	pathogenic	-0.264	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
N/Y	0.9956	likely_pathogenic	0.9939	pathogenic	0.399	Stabilizing	1.0	D	0.879	deleterious	D	0.797937254	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.