TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1144	3655;3656;3657	chr2:178781214;178781213;178781212	chr2:179645941;179645940;179645939
N2AB	1144	3655;3656;3657	chr2:178781214;178781213;178781212	chr2:179645941;179645940;179645939
N2A	1144	3655;3656;3657	chr2:178781214;178781213;178781212	chr2:179645941;179645940;179645939
N2B	1098	3517;3518;3519	chr2:178781214;178781213;178781212	chr2:179645941;179645940;179645939
Novex-1	1098	3517;3518;3519	chr2:178781214;178781213;178781212	chr2:179645941;179645940;179645939
Novex-2	1098	3517;3518;3519	chr2:178781214;178781213;178781212	chr2:179645941;179645940;179645939
Novex-3	1144	3655;3656;3657	chr2:178781214;178781213;178781212	chr2:179645941;179645940;179645939

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-4
• Domain position: 63
• Structural Position: 141
• Q(SASA): 0.3634
• 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/P	None	None	1.0	N	0.673	0.706	0.530211221528	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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	0.1806	likely_benign	0.1749	benign	-0.803	Destabilizing	0.997	D	0.429	neutral	N	0.489198032	None	None	I
S/C	0.4763	ambiguous	0.4481	ambiguous	-0.678	Destabilizing	1.0	D	0.626	neutral	N	0.514075182	None	None	I
S/D	0.8075	likely_pathogenic	0.8253	pathogenic	-0.656	Destabilizing	0.999	D	0.563	neutral	None	None	None	None	I
S/E	0.872	likely_pathogenic	0.883	pathogenic	-0.663	Destabilizing	0.999	D	0.547	neutral	None	None	None	None	I
S/F	0.5649	likely_pathogenic	0.5953	pathogenic	-1.121	Destabilizing	1.0	D	0.679	prob.neutral	N	0.511920377	None	None	I
S/G	0.2671	likely_benign	0.2515	benign	-1.024	Destabilizing	0.999	D	0.459	neutral	None	None	None	None	I
S/H	0.7312	likely_pathogenic	0.7341	pathogenic	-1.525	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	I
S/I	0.6771	likely_pathogenic	0.6624	pathogenic	-0.32	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	I
S/K	0.9642	likely_pathogenic	0.9678	pathogenic	-0.705	Destabilizing	0.999	D	0.554	neutral	None	None	None	None	I
S/L	0.3131	likely_benign	0.3063	benign	-0.32	Destabilizing	1.0	D	0.596	neutral	None	None	None	None	I
S/M	0.5149	ambiguous	0.5061	ambiguous	0.051	Stabilizing	1.0	D	0.651	neutral	None	None	None	None	I
S/N	0.3985	ambiguous	0.3762	ambiguous	-0.738	Destabilizing	0.999	D	0.534	neutral	None	None	None	None	I
S/P	0.8782	likely_pathogenic	0.8169	pathogenic	-0.45	Destabilizing	1.0	D	0.673	neutral	N	0.496472565	None	None	I
S/Q	0.8309	likely_pathogenic	0.8356	pathogenic	-0.981	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	I
S/R	0.9383	likely_pathogenic	0.9412	pathogenic	-0.538	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	I
S/T	0.195	likely_benign	0.1956	benign	-0.743	Destabilizing	0.999	D	0.443	neutral	N	0.462091808	None	None	I
S/V	0.626	likely_pathogenic	0.6143	pathogenic	-0.45	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	I
S/W	0.7598	likely_pathogenic	0.7598	pathogenic	-1.071	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	I
S/Y	0.5047	ambiguous	0.5308	ambiguous	-0.791	Destabilizing	1.0	D	0.676	prob.neutral	N	0.499204208	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.