TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15405	46438;46439;46440	chr2:178620308;178620307;178620306	chr2:179485035;179485034;179485033
N2AB	13764	41515;41516;41517	chr2:178620308;178620307;178620306	chr2:179485035;179485034;179485033
N2A	12837	38734;38735;38736	chr2:178620308;178620307;178620306	chr2:179485035;179485034;179485033
N2B	6340	19243;19244;19245	chr2:178620308;178620307;178620306	chr2:179485035;179485034;179485033
Novex-1	6465	19618;19619;19620	chr2:178620308;178620307;178620306	chr2:179485035;179485034;179485033
Novex-2	6532	19819;19820;19821	chr2:178620308;178620307;178620306	chr2:179485035;179485034;179485033
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-106
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.6611
• 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
F/L	rs779560487	None	0.999	N	0.653	0.508	0.283761946502	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	2.88517E-04	0	None	0	0	0	0	0
F/L	rs779560487	None	0.999	N	0.653	0.508	0.283761946502	gnomAD-4.0.0	6.58415E-06	None	None	None	None	N	None	0	0	None	2.88517E-04	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
F/A	0.8136	likely_pathogenic	0.8017	pathogenic	-1.092	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
F/C	0.7311	likely_pathogenic	0.6881	pathogenic	-0.132	Destabilizing	1.0	D	0.751	deleterious	N	0.504105685	None	None	N
F/D	0.8241	likely_pathogenic	0.8213	pathogenic	0.409	Stabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
F/E	0.9025	likely_pathogenic	0.8933	pathogenic	0.372	Stabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
F/G	0.7317	likely_pathogenic	0.6857	pathogenic	-1.298	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	N
F/H	0.7567	likely_pathogenic	0.7573	pathogenic	0.073	Stabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
F/I	0.8154	likely_pathogenic	0.8177	pathogenic	-0.564	Destabilizing	1.0	D	0.717	prob.delet.	N	0.503896204	None	None	N
F/K	0.9069	likely_pathogenic	0.882	pathogenic	-0.06	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
F/L	0.9537	likely_pathogenic	0.95	pathogenic	-0.564	Destabilizing	0.999	D	0.653	neutral	N	0.504987561	None	None	N
F/M	0.7625	likely_pathogenic	0.7402	pathogenic	-0.282	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
F/N	0.6129	likely_pathogenic	0.6067	pathogenic	0.085	Stabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
F/P	0.9966	likely_pathogenic	0.9965	pathogenic	-0.72	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
F/Q	0.8966	likely_pathogenic	0.8822	pathogenic	-0.064	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
F/R	0.8697	likely_pathogenic	0.8447	pathogenic	0.514	Stabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
F/S	0.6519	likely_pathogenic	0.651	pathogenic	-0.575	Destabilizing	1.0	D	0.7	prob.neutral	N	0.472926702	None	None	N
F/T	0.7569	likely_pathogenic	0.7237	pathogenic	-0.519	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
F/V	0.772	likely_pathogenic	0.7652	pathogenic	-0.72	Destabilizing	1.0	D	0.729	prob.delet.	N	0.505400675	None	None	N
F/W	0.6192	likely_pathogenic	0.6289	pathogenic	-0.497	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
F/Y	0.1918	likely_benign	0.2014	benign	-0.423	Destabilizing	0.999	D	0.66	neutral	N	0.505400675	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.