TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26320	79183;79184;79185	chr2:178567174;178567173;178567172	chr2:179431901;179431900;179431899
N2AB	24679	74260;74261;74262	chr2:178567174;178567173;178567172	chr2:179431901;179431900;179431899
N2A	23752	71479;71480;71481	chr2:178567174;178567173;178567172	chr2:179431901;179431900;179431899
N2B	17255	51988;51989;51990	chr2:178567174;178567173;178567172	chr2:179431901;179431900;179431899
Novex-1	17380	52363;52364;52365	chr2:178567174;178567173;178567172	chr2:179431901;179431900;179431899
Novex-2	17447	52564;52565;52566	chr2:178567174;178567173;178567172	chr2:179431901;179431900;179431899
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-79
• Domain position: 35
• Structural Position: 36
• Q(SASA): 0.3293
• 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
S/C	None	None	0.999	N	0.706	0.47	0.504789117978	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	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
S/A	0.1304	likely_benign	0.1202	benign	-0.528	Destabilizing	0.773	D	0.431	neutral	N	0.467254181	None	None	I
S/C	0.1579	likely_benign	0.1456	benign	-0.349	Destabilizing	0.999	D	0.706	prob.neutral	N	0.477422399	None	None	I
S/D	0.6448	likely_pathogenic	0.5617	ambiguous	-0.113	Destabilizing	0.916	D	0.507	neutral	None	None	None	None	I
S/E	0.726	likely_pathogenic	0.6686	pathogenic	-0.12	Destabilizing	0.845	D	0.469	neutral	None	None	None	None	I
S/F	0.3118	likely_benign	0.278	benign	-0.668	Destabilizing	0.994	D	0.765	deleterious	N	0.495019675	None	None	I
S/G	0.1586	likely_benign	0.1579	benign	-0.78	Destabilizing	0.916	D	0.469	neutral	None	None	None	None	I
S/H	0.5314	ambiguous	0.48	ambiguous	-1.274	Destabilizing	0.997	D	0.717	prob.delet.	None	None	None	None	I
S/I	0.2418	likely_benign	0.2116	benign	0.029	Stabilizing	0.987	D	0.778	deleterious	None	None	None	None	I
S/K	0.8301	likely_pathogenic	0.7761	pathogenic	-0.729	Destabilizing	0.845	D	0.471	neutral	None	None	None	None	I
S/L	0.1092	likely_benign	0.1082	benign	0.029	Stabilizing	0.916	D	0.653	neutral	None	None	None	None	I
S/M	0.2074	likely_benign	0.1979	benign	0.192	Stabilizing	0.997	D	0.717	prob.delet.	None	None	None	None	I
S/N	0.243	likely_benign	0.2445	benign	-0.628	Destabilizing	0.916	D	0.53	neutral	None	None	None	None	I
S/P	0.8697	likely_pathogenic	0.8476	pathogenic	-0.122	Destabilizing	0.983	D	0.746	deleterious	N	0.506882959	None	None	I
S/Q	0.6488	likely_pathogenic	0.614	pathogenic	-0.729	Destabilizing	0.253	N	0.207	neutral	None	None	None	None	I
S/R	0.8053	likely_pathogenic	0.7499	pathogenic	-0.646	Destabilizing	0.95	D	0.673	neutral	None	None	None	None	I
S/T	0.0651	likely_benign	0.0629	benign	-0.618	Destabilizing	0.892	D	0.455	neutral	N	0.37756405	None	None	I
S/V	0.2554	likely_benign	0.2259	benign	-0.122	Destabilizing	0.975	D	0.654	neutral	None	None	None	None	I
S/W	0.5727	likely_pathogenic	0.4853	ambiguous	-0.703	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	I
S/Y	0.3338	likely_benign	0.2847	benign	-0.433	Destabilizing	0.994	D	0.77	deleterious	N	0.488525215	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.