TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14730	44413;44414;44415	chr2:178630334;178630333;178630332	chr2:179495061;179495060;179495059
N2AB	13089	39490;39491;39492	chr2:178630334;178630333;178630332	chr2:179495061;179495060;179495059
N2A	12162	36709;36710;36711	chr2:178630334;178630333;178630332	chr2:179495061;179495060;179495059
N2B	5665	17218;17219;17220	chr2:178630334;178630333;178630332	chr2:179495061;179495060;179495059
Novex-1	5790	17593;17594;17595	chr2:178630334;178630333;178630332	chr2:179495061;179495060;179495059
Novex-2	5857	17794;17795;17796	chr2:178630334;178630333;178630332	chr2:179495061;179495060;179495059
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-98
• Domain position: 56
• Structural Position: 137
• Q(SASA): 0.2307
• 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	None	N	0.283	0.046	0.210429274316	gnomAD-4.0.0	1.59593E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86302E-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	0.092	likely_benign	0.0916	benign	-0.636	Destabilizing	0.001	N	0.303	neutral	N	0.437802437	None	None	N
S/C	0.0507	likely_benign	0.0586	benign	-0.541	Destabilizing	None	N	0.378	neutral	N	0.437048332	None	None	N
S/D	0.4962	ambiguous	0.4213	ambiguous	-1.593	Destabilizing	0.017	N	0.429	neutral	None	None	None	None	N
S/E	0.4763	ambiguous	0.4546	ambiguous	-1.37	Destabilizing	0.017	N	0.433	neutral	None	None	None	None	N
S/F	0.0483	likely_benign	0.0568	benign	-0.341	Destabilizing	None	N	0.283	neutral	N	0.402710675	None	None	N
S/G	0.1715	likely_benign	0.1596	benign	-1.057	Destabilizing	0.008	N	0.471	neutral	None	None	None	None	N
S/H	0.1409	likely_benign	0.1642	benign	-1.451	Destabilizing	0.131	N	0.469	neutral	None	None	None	None	N
S/I	0.0762	likely_benign	0.0778	benign	0.444	Stabilizing	None	N	0.366	neutral	None	None	None	None	N
S/K	0.4987	ambiguous	0.5043	ambiguous	-0.331	Destabilizing	0.017	N	0.441	neutral	None	None	None	None	N
S/L	0.0938	likely_benign	0.0906	benign	0.444	Stabilizing	None	N	0.435	neutral	None	None	None	None	N
S/M	0.1349	likely_benign	0.1442	benign	0.188	Stabilizing	None	N	0.313	neutral	None	None	None	None	N
S/N	0.162	likely_benign	0.1537	benign	-1.12	Destabilizing	0.017	N	0.405	neutral	None	None	None	None	N
S/P	0.9661	likely_pathogenic	0.9447	pathogenic	0.119	Stabilizing	0.09	N	0.549	neutral	N	0.440029136	None	None	N
S/Q	0.3199	likely_benign	0.357	ambiguous	-0.751	Destabilizing	0.041	N	0.484	neutral	None	None	None	None	N
S/R	0.3253	likely_benign	0.3322	benign	-0.819	Destabilizing	0.041	N	0.552	neutral	None	None	None	None	N
S/T	0.0727	likely_benign	0.073	benign	-0.697	Destabilizing	None	N	0.183	neutral	N	0.366462325	None	None	N
S/V	0.0884	likely_benign	0.0858	benign	0.119	Stabilizing	None	N	0.283	neutral	None	None	None	None	N
S/W	0.1423	likely_benign	0.1419	benign	-0.754	Destabilizing	0.131	N	0.531	neutral	None	None	None	None	N
S/Y	0.0563	likely_benign	0.062	benign	-0.244	Destabilizing	0.003	N	0.489	neutral	N	0.438616853	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.