TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29398	88417;88418;88419	chr2:178556962;178556961;178556960	chr2:179421689;179421688;179421687
N2AB	27757	83494;83495;83496	chr2:178556962;178556961;178556960	chr2:179421689;179421688;179421687
N2A	26830	80713;80714;80715	chr2:178556962;178556961;178556960	chr2:179421689;179421688;179421687
N2B	20333	61222;61223;61224	chr2:178556962;178556961;178556960	chr2:179421689;179421688;179421687
Novex-1	20458	61597;61598;61599	chr2:178556962;178556961;178556960	chr2:179421689;179421688;179421687
Novex-2	20525	61798;61799;61800	chr2:178556962;178556961;178556960	chr2:179421689;179421688;179421687
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: Fn3-102
• Domain position: 64
• Structural Position: 94
• Q(SASA): 0.6316
• 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/A	None	None	0.349	N	0.319	0.083	0.151104730317	gnomAD-4.0.0	6.8421E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	1.7343E-04	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
S/A	0.1003	likely_benign	0.0865	benign	-0.342	Destabilizing	0.349	N	0.319	neutral	N	0.496202162	None	None	N
S/C	0.1623	likely_benign	0.1344	benign	-0.382	Destabilizing	0.995	D	0.632	neutral	N	0.473676644	None	None	N
S/D	0.4702	ambiguous	0.4221	ambiguous	0.497	Stabilizing	0.775	D	0.411	neutral	None	None	None	None	N
S/E	0.5987	likely_pathogenic	0.5465	ambiguous	0.411	Stabilizing	0.775	D	0.399	neutral	None	None	None	None	N
S/F	0.3393	likely_benign	0.2734	benign	-0.994	Destabilizing	0.949	D	0.706	prob.neutral	N	0.469295324	None	None	N
S/G	0.0928	likely_benign	0.0897	benign	-0.434	Destabilizing	0.775	D	0.413	neutral	None	None	None	None	N
S/H	0.3998	ambiguous	0.3607	ambiguous	-0.834	Destabilizing	0.996	D	0.633	neutral	None	None	None	None	N
S/I	0.3338	likely_benign	0.2716	benign	-0.23	Destabilizing	0.858	D	0.641	neutral	None	None	None	None	N
S/K	0.7115	likely_pathogenic	0.6584	pathogenic	-0.276	Destabilizing	0.775	D	0.409	neutral	None	None	None	None	N
S/L	0.1365	likely_benign	0.1125	benign	-0.23	Destabilizing	0.633	D	0.552	neutral	None	None	None	None	N
S/M	0.2666	likely_benign	0.2385	benign	-0.159	Destabilizing	0.989	D	0.641	neutral	None	None	None	None	N
S/N	0.1521	likely_benign	0.1408	benign	-0.114	Destabilizing	0.775	D	0.422	neutral	None	None	None	None	N
S/P	0.1198	likely_benign	0.1096	benign	-0.24	Destabilizing	0.949	D	0.603	neutral	N	0.485081091	None	None	N
S/Q	0.5636	ambiguous	0.5229	ambiguous	-0.292	Destabilizing	0.961	D	0.527	neutral	None	None	None	None	N
S/R	0.6659	likely_pathogenic	0.6109	pathogenic	-0.126	Destabilizing	0.923	D	0.609	neutral	None	None	None	None	N
S/T	0.0768	likely_benign	0.0692	benign	-0.24	Destabilizing	0.001	N	0.173	neutral	N	0.352111032	None	None	N
S/V	0.3016	likely_benign	0.2467	benign	-0.24	Destabilizing	0.633	D	0.554	neutral	None	None	None	None	N
S/W	0.4664	ambiguous	0.3893	ambiguous	-1.017	Destabilizing	0.996	D	0.74	deleterious	None	None	None	None	N
S/Y	0.2648	likely_benign	0.2233	benign	-0.707	Destabilizing	0.949	D	0.707	prob.neutral	N	0.50982482	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.