TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23360	70303;70304;70305	chr2:178576054;178576053;178576052	chr2:179440781;179440780;179440779
N2AB	21719	65380;65381;65382	chr2:178576054;178576053;178576052	chr2:179440781;179440780;179440779
N2A	20792	62599;62600;62601	chr2:178576054;178576053;178576052	chr2:179440781;179440780;179440779
N2B	14295	43108;43109;43110	chr2:178576054;178576053;178576052	chr2:179440781;179440780;179440779
Novex-1	14420	43483;43484;43485	chr2:178576054;178576053;178576052	chr2:179440781;179440780;179440779
Novex-2	14487	43684;43685;43686	chr2:178576054;178576053;178576052	chr2:179440781;179440780;179440779
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-129
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.3445
• 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
L/F	None	None	0.007	N	0.19	0.075	0.27855597813	gnomAD-4.0.0	6.84307E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.09625E-06	0	1.65684E-05

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
L/A	0.1825	likely_benign	0.1989	benign	-0.65	Destabilizing	0.373	N	0.289	neutral	None	None	None	None	I
L/C	0.339	likely_benign	0.3324	benign	-0.644	Destabilizing	0.02	N	0.27	neutral	None	None	None	None	I
L/D	0.6829	likely_pathogenic	0.6783	pathogenic	0.103	Stabilizing	0.009	N	0.313	neutral	None	None	None	None	I
L/E	0.436	ambiguous	0.4217	ambiguous	0.022	Stabilizing	0.59	D	0.397	neutral	None	None	None	None	I
L/F	0.183	likely_benign	0.2089	benign	-0.605	Destabilizing	0.007	N	0.19	neutral	N	0.461344935	None	None	I
L/G	0.3502	ambiguous	0.3621	ambiguous	-0.831	Destabilizing	0.742	D	0.419	neutral	None	None	None	None	I
L/H	0.2581	likely_benign	0.2649	benign	-0.105	Destabilizing	0.994	D	0.377	neutral	N	0.423383979	None	None	I
L/I	0.1447	likely_benign	0.1621	benign	-0.293	Destabilizing	0.684	D	0.264	neutral	N	0.461344935	None	None	I
L/K	0.3389	likely_benign	0.3267	benign	-0.261	Destabilizing	0.91	D	0.403	neutral	None	None	None	None	I
L/M	0.0977	likely_benign	0.104	benign	-0.326	Destabilizing	0.984	D	0.32	neutral	None	None	None	None	I
L/N	0.2676	likely_benign	0.2603	benign	-0.059	Destabilizing	0.835	D	0.414	neutral	None	None	None	None	I
L/P	0.8995	likely_pathogenic	0.9057	pathogenic	-0.378	Destabilizing	0.939	D	0.407	neutral	N	0.460998218	None	None	I
L/Q	0.1641	likely_benign	0.1537	benign	-0.265	Destabilizing	0.953	D	0.381	neutral	None	None	None	None	I
L/R	0.3104	likely_benign	0.3197	benign	0.254	Stabilizing	0.939	D	0.385	neutral	N	0.422863904	None	None	I
L/S	0.2143	likely_benign	0.2273	benign	-0.595	Destabilizing	0.59	D	0.359	neutral	None	None	None	None	I
L/T	0.2008	likely_benign	0.203	benign	-0.56	Destabilizing	0.037	N	0.234	neutral	None	None	None	None	I
L/V	0.1131	likely_benign	0.1271	benign	-0.378	Destabilizing	0.472	N	0.288	neutral	N	0.383057509	None	None	I
L/W	0.4508	ambiguous	0.4839	ambiguous	-0.607	Destabilizing	0.996	D	0.369	neutral	None	None	None	None	I
L/Y	0.343	ambiguous	0.3632	ambiguous	-0.349	Destabilizing	0.835	D	0.329	neutral	None	None	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.