TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23534	70825;70826;70827	chr2:178575532;178575531;178575530	chr2:179440259;179440258;179440257
N2AB	21893	65902;65903;65904	chr2:178575532;178575531;178575530	chr2:179440259;179440258;179440257
N2A	20966	63121;63122;63123	chr2:178575532;178575531;178575530	chr2:179440259;179440258;179440257
N2B	14469	43630;43631;43632	chr2:178575532;178575531;178575530	chr2:179440259;179440258;179440257
Novex-1	14594	44005;44006;44007	chr2:178575532;178575531;178575530	chr2:179440259;179440258;179440257
Novex-2	14661	44206;44207;44208	chr2:178575532;178575531;178575530	chr2:179440259;179440258;179440257
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: Fn3-59
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.239
• 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	0.331	N	0.767	0.218	0.367612772649	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
S/A	0.0856	likely_benign	0.0897	benign	-0.611	Destabilizing	0.104	N	0.503	neutral	N	0.475895597	None	None	N
S/C	0.1297	likely_benign	0.1399	benign	-0.559	Destabilizing	0.002	N	0.609	neutral	N	0.510524399	None	None	N
S/D	0.5153	ambiguous	0.566	pathogenic	-1.087	Destabilizing	0.89	D	0.529	neutral	None	None	None	None	N
S/E	0.5301	ambiguous	0.6133	pathogenic	-1.05	Destabilizing	0.726	D	0.512	neutral	None	None	None	None	N
S/F	0.1872	likely_benign	0.2114	benign	-0.645	Destabilizing	0.331	N	0.767	deleterious	N	0.510270909	None	None	N
S/G	0.1101	likely_benign	0.1119	benign	-0.901	Destabilizing	0.431	N	0.456	neutral	None	None	None	None	N
S/H	0.4603	ambiguous	0.5386	ambiguous	-1.474	Destabilizing	0.968	D	0.689	prob.neutral	None	None	None	None	N
S/I	0.2912	likely_benign	0.3022	benign	0.064	Stabilizing	0.157	N	0.726	prob.delet.	None	None	None	None	N
S/K	0.7801	likely_pathogenic	0.8495	pathogenic	-0.912	Destabilizing	0.431	N	0.511	neutral	None	None	None	None	N
S/L	0.0587	likely_benign	0.0651	benign	0.064	Stabilizing	None	N	0.535	neutral	None	None	None	None	N
S/M	0.1435	likely_benign	0.1715	benign	0.322	Stabilizing	0.396	N	0.686	prob.neutral	None	None	None	None	N
S/N	0.2553	likely_benign	0.2563	benign	-1.052	Destabilizing	0.89	D	0.53	neutral	None	None	None	None	N
S/P	0.7947	likely_pathogenic	0.8048	pathogenic	-0.126	Destabilizing	0.859	D	0.687	prob.neutral	N	0.505454609	None	None	N
S/Q	0.5037	ambiguous	0.6047	pathogenic	-1.151	Destabilizing	0.89	D	0.539	neutral	None	None	None	None	N
S/R	0.7802	likely_pathogenic	0.841	pathogenic	-0.876	Destabilizing	0.726	D	0.688	prob.neutral	None	None	None	None	N
S/T	0.1037	likely_benign	0.1024	benign	-0.889	Destabilizing	0.22	N	0.48	neutral	N	0.496783739	None	None	N
S/V	0.2248	likely_benign	0.2465	benign	-0.126	Destabilizing	0.157	N	0.696	prob.neutral	None	None	None	None	N
S/W	0.3808	ambiguous	0.4429	ambiguous	-0.74	Destabilizing	0.968	D	0.818	deleterious	None	None	None	None	N
S/Y	0.213	likely_benign	0.241	benign	-0.432	Destabilizing	0.667	D	0.772	deleterious	N	0.51001742	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.