TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24285	73078;73079;73080	chr2:178573279;178573278;178573277	chr2:179438006;179438005;179438004
N2AB	22644	68155;68156;68157	chr2:178573279;178573278;178573277	chr2:179438006;179438005;179438004
N2A	21717	65374;65375;65376	chr2:178573279;178573278;178573277	chr2:179438006;179438005;179438004
N2B	15220	45883;45884;45885	chr2:178573279;178573278;178573277	chr2:179438006;179438005;179438004
Novex-1	15345	46258;46259;46260	chr2:178573279;178573278;178573277	chr2:179438006;179438005;179438004
Novex-2	15412	46459;46460;46461	chr2:178573279;178573278;178573277	chr2:179438006;179438005;179438004
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: Fn3-64
• Domain position: 64
• Structural Position: 94
• Q(SASA): 0.5016
• 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
S/F	None	None	0.983	N	0.771	0.476	0.715032251236	gnomAD-4.0.0	6.9043E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.04819E-07	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	0.0725	likely_benign	0.0681	benign	-0.595	Destabilizing	0.63	D	0.39	neutral	N	0.514249205	None	None	N
S/C	0.098	likely_benign	0.0949	benign	-0.333	Destabilizing	0.999	D	0.716	prob.delet.	N	0.475157901	None	None	N
S/D	0.629	likely_pathogenic	0.5862	pathogenic	-0.006	Destabilizing	0.916	D	0.513	neutral	None	None	None	None	N
S/E	0.7063	likely_pathogenic	0.6786	pathogenic	-0.077	Destabilizing	0.916	D	0.518	neutral	None	None	None	None	N
S/F	0.1936	likely_benign	0.182	benign	-1.035	Destabilizing	0.983	D	0.771	deleterious	N	0.485753738	None	None	N
S/G	0.0816	likely_benign	0.0786	benign	-0.756	Destabilizing	0.916	D	0.449	neutral	None	None	None	None	N
S/H	0.4004	ambiguous	0.3819	ambiguous	-1.233	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
S/I	0.1521	likely_benign	0.1409	benign	-0.29	Destabilizing	0.975	D	0.752	deleterious	None	None	None	None	N
S/K	0.7518	likely_pathogenic	0.7283	pathogenic	-0.652	Destabilizing	0.916	D	0.515	neutral	None	None	None	None	N
S/L	0.0808	likely_benign	0.079	benign	-0.29	Destabilizing	0.845	D	0.623	neutral	None	None	None	None	N
S/M	0.1424	likely_benign	0.1437	benign	0.054	Stabilizing	0.997	D	0.713	prob.delet.	None	None	None	None	N
S/N	0.1442	likely_benign	0.1337	benign	-0.386	Destabilizing	0.916	D	0.517	neutral	None	None	None	None	N
S/P	0.1368	likely_benign	0.1372	benign	-0.361	Destabilizing	0.983	D	0.74	deleterious	N	0.493700574	None	None	N
S/Q	0.5366	ambiguous	0.5176	ambiguous	-0.633	Destabilizing	0.987	D	0.617	neutral	None	None	None	None	N
S/R	0.7186	likely_pathogenic	0.6931	pathogenic	-0.42	Destabilizing	0.975	D	0.745	deleterious	None	None	None	None	N
S/T	0.058	likely_benign	0.0603	benign	-0.489	Destabilizing	0.011	N	0.221	neutral	N	0.379585635	None	None	N
S/V	0.1489	likely_benign	0.1407	benign	-0.361	Destabilizing	0.845	D	0.633	neutral	None	None	None	None	N
S/W	0.3596	ambiguous	0.3535	ambiguous	-0.997	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
S/Y	0.2052	likely_benign	0.1941	benign	-0.75	Destabilizing	0.994	D	0.763	deleterious	N	0.486007227	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.