TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5316	16171;16172;16173	chr2:178733347;178733346;178733345	chr2:179598074;179598073;179598072
N2AB	4999	15220;15221;15222	chr2:178733347;178733346;178733345	chr2:179598074;179598073;179598072
N2A	4072	12439;12440;12441	chr2:178733347;178733346;178733345	chr2:179598074;179598073;179598072
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: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-36
• Domain position: 56
• Structural Position: 136
• Q(SASA): 0.0527
• 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
A/V	rs879242937	0.903	0.996	N	0.647	0.311	None	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.67E-05	0
A/V	rs879242937	0.903	0.996	N	0.647	0.311	None	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	5.88E-05	0	0
A/V	rs879242937	0.903	0.996	N	0.647	0.311	None	gnomAD-4.0.0	2.78862E-05	None	None	None	None	N	None	1.33476E-05	0	None	0	0	None	0	0	3.47515E-05	0	4.80369E-05

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
A/C	0.6753	likely_pathogenic	0.6619	pathogenic	-0.106	Destabilizing	0.844	D	0.515	neutral	None	None	None	None	N
A/D	0.9826	likely_pathogenic	0.985	pathogenic	-1.769	Destabilizing	1.0	D	0.831	deleterious	D	0.561059366	None	None	N
A/E	0.962	likely_pathogenic	0.9662	pathogenic	-1.44	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
A/F	0.8057	likely_pathogenic	0.813	pathogenic	0.008	Stabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
A/G	0.3439	ambiguous	0.3481	ambiguous	-0.941	Destabilizing	0.998	D	0.636	neutral	N	0.454508203	None	None	N
A/H	0.9635	likely_pathogenic	0.9671	pathogenic	-1.759	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
A/I	0.6475	likely_pathogenic	0.6547	pathogenic	1.329	Stabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
A/K	0.9874	likely_pathogenic	0.9908	pathogenic	-0.028	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
A/L	0.5508	ambiguous	0.5625	ambiguous	1.329	Stabilizing	0.997	D	0.703	prob.neutral	None	None	None	None	N
A/M	0.6414	likely_pathogenic	0.6468	pathogenic	0.7	Stabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
A/N	0.944	likely_pathogenic	0.9438	pathogenic	-0.748	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
A/P	0.9727	likely_pathogenic	0.9768	pathogenic	0.811	Stabilizing	1.0	D	0.835	deleterious	D	0.622582501	None	None	N
A/Q	0.929	likely_pathogenic	0.939	pathogenic	-0.24	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
A/R	0.9628	likely_pathogenic	0.9737	pathogenic	-0.844	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
A/S	0.2346	likely_benign	0.1987	benign	-1.036	Destabilizing	0.998	D	0.642	neutral	N	0.414102816	None	None	N
A/T	0.3401	ambiguous	0.3089	benign	-0.536	Destabilizing	0.999	D	0.739	prob.delet.	N	0.443266406	None	None	N
A/V	0.3528	ambiguous	0.3499	ambiguous	0.811	Stabilizing	0.996	D	0.647	neutral	N	0.467633291	None	None	N
A/W	0.977	likely_pathogenic	0.9797	pathogenic	-0.837	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
A/Y	0.9198	likely_pathogenic	0.9279	pathogenic	-0.193	Destabilizing	1.0	D	0.843	deleterious	None	None	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.