TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5137	15634;15635;15636	chr2:178734415;178734414;178734413	chr2:179599142;179599141;179599140
N2AB	4820	14683;14684;14685	chr2:178734415;178734414;178734413	chr2:179599142;179599141;179599140
N2A	3893	11902;11903;11904	chr2:178734415;178734414;178734413	chr2:179599142;179599141;179599140
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-34
• Domain position: 63
• Structural Position: 144
• Q(SASA): 0.0922
• 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
F/L	rs1417172594	-1.89	0.999	N	0.5	0.437	0.376921832658	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	1.29216E-04	0	None	0	0	None	0	None	0	0	0
F/L	rs1417172594	-1.89	0.999	N	0.5	0.437	0.376921832658	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
F/L	rs1417172594	-1.89	0.999	N	0.5	0.437	0.376921832658	gnomAD-4.0.0	2.56245E-06	None	None	None	None	N	None	3.38318E-05	0	None	0	0	None	0	0	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
F/A	0.7835	likely_pathogenic	0.836	pathogenic	-2.455	Highly Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
F/C	0.3442	ambiguous	0.4537	ambiguous	-2.676	Highly Destabilizing	1.0	D	0.697	prob.neutral	N	0.469923524	None	None	N
F/D	0.9884	likely_pathogenic	0.9927	pathogenic	-2.698	Highly Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
F/E	0.9881	likely_pathogenic	0.9918	pathogenic	-2.601	Highly Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
F/G	0.9193	likely_pathogenic	0.9482	pathogenic	-2.778	Highly Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
F/H	0.8941	likely_pathogenic	0.9338	pathogenic	-1.38	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
F/I	0.4535	ambiguous	0.4994	ambiguous	-1.453	Destabilizing	1.0	D	0.731	prob.delet.	N	0.478989472	None	None	N
F/K	0.9894	likely_pathogenic	0.9929	pathogenic	-1.858	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
F/L	0.9116	likely_pathogenic	0.9209	pathogenic	-1.453	Destabilizing	0.999	D	0.5	neutral	N	0.421622848	None	None	N
F/M	0.7095	likely_pathogenic	0.734	pathogenic	-1.737	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
F/N	0.9287	likely_pathogenic	0.9531	pathogenic	-2.046	Highly Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
F/P	0.9771	likely_pathogenic	0.984	pathogenic	-1.787	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
F/Q	0.967	likely_pathogenic	0.9797	pathogenic	-2.227	Highly Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
F/R	0.9688	likely_pathogenic	0.9798	pathogenic	-1.17	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
F/S	0.7358	likely_pathogenic	0.8121	pathogenic	-2.757	Highly Destabilizing	1.0	D	0.719	prob.delet.	N	0.506011504	None	None	N
F/T	0.8199	likely_pathogenic	0.8547	pathogenic	-2.558	Highly Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
F/V	0.333	likely_benign	0.3803	ambiguous	-1.787	Destabilizing	1.0	D	0.683	prob.neutral	N	0.381676516	None	None	N
F/W	0.7413	likely_pathogenic	0.7985	pathogenic	-0.757	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
F/Y	0.2831	likely_benign	0.3605	ambiguous	-0.876	Destabilizing	0.999	D	0.55	neutral	D	0.548198286	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.