TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31605	95038;95039;95040	chr2:178546615;178546614;178546613	chr2:179411342;179411341;179411340
N2AB	29964	90115;90116;90117	chr2:178546615;178546614;178546613	chr2:179411342;179411341;179411340
N2A	29037	87334;87335;87336	chr2:178546615;178546614;178546613	chr2:179411342;179411341;179411340
N2B	22540	67843;67844;67845	chr2:178546615;178546614;178546613	chr2:179411342;179411341;179411340
Novex-1	22665	68218;68219;68220	chr2:178546615;178546614;178546613	chr2:179411342;179411341;179411340
Novex-2	22732	68419;68420;68421	chr2:178546615;178546614;178546613	chr2:179411342;179411341;179411340
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Fn3-118
• Domain position: 100
• Structural Position: 130
• Q(SASA): 0.0583
• 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
C/S	rs1308471692	None	0.999	N	0.837	0.512	0.618750016433	gnomAD-4.0.0	1.60349E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.89041E-06	0	0
C/Y	rs991386516	None	0.999	N	0.832	0.362	0.68565156927	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
C/A	0.7768	likely_pathogenic	0.7586	pathogenic	-0.166	Destabilizing	0.995	D	0.606	neutral	None	None	None	None	N
C/D	0.9995	likely_pathogenic	0.9994	pathogenic	-1.414	Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
C/E	0.9996	likely_pathogenic	0.9995	pathogenic	-1.297	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
C/F	0.9604	likely_pathogenic	0.9566	pathogenic	-0.545	Destabilizing	0.999	D	0.836	deleterious	N	0.486121088	None	None	N
C/G	0.8788	likely_pathogenic	0.8498	pathogenic	-0.367	Destabilizing	0.999	D	0.809	deleterious	N	0.489162962	None	None	N
C/H	0.9983	likely_pathogenic	0.998	pathogenic	-1.22	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
C/I	0.8356	likely_pathogenic	0.8316	pathogenic	0.287	Stabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
C/K	0.9997	likely_pathogenic	0.9996	pathogenic	0.058	Stabilizing	0.999	D	0.811	deleterious	None	None	None	None	N
C/L	0.8635	likely_pathogenic	0.854	pathogenic	0.287	Stabilizing	0.998	D	0.718	prob.delet.	None	None	None	None	N
C/M	0.9717	likely_pathogenic	0.9703	pathogenic	0.304	Stabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
C/N	0.9944	likely_pathogenic	0.9932	pathogenic	-0.4	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
C/P	0.9555	likely_pathogenic	0.95	pathogenic	0.162	Stabilizing	0.999	D	0.8	deleterious	None	None	None	None	N
C/Q	0.9983	likely_pathogenic	0.9979	pathogenic	-0.3	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
C/R	0.9947	likely_pathogenic	0.9937	pathogenic	-0.35	Destabilizing	0.999	D	0.79	deleterious	N	0.489416452	None	None	N
C/S	0.9072	likely_pathogenic	0.8945	pathogenic	-0.348	Destabilizing	0.999	D	0.837	deleterious	N	0.476881604	None	None	N
C/T	0.9075	likely_pathogenic	0.9107	pathogenic	-0.102	Destabilizing	0.999	D	0.833	deleterious	None	None	None	None	N
C/V	0.6352	likely_pathogenic	0.6321	pathogenic	0.162	Stabilizing	0.998	D	0.731	deleterious	None	None	None	None	N
C/W	0.9966	likely_pathogenic	0.9965	pathogenic	-1.11	Destabilizing	1.0	D	0.8	deleterious	N	0.490176921	None	None	N
C/Y	0.9934	likely_pathogenic	0.992	pathogenic	-0.561	Destabilizing	0.999	D	0.832	deleterious	N	0.488909473	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.