TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5150	15673;15674;15675	chr2:178734376;178734375;178734374	chr2:179599103;179599102;179599101
N2AB	4833	14722;14723;14724	chr2:178734376;178734375;178734374	chr2:179599103;179599102;179599101
N2A	3906	11941;11942;11943	chr2:178734376;178734375;178734374	chr2:179599103;179599102;179599101
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: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-34
• Domain position: 76
• Structural Position: 159
• Q(SASA): 0.1525
• 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/T	None	None	0.956	N	0.617	0.284	0.402899589544	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
A/V	None	None	0.989	N	0.672	0.387	0.65763613582	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
A/C	0.4632	ambiguous	0.4782	ambiguous	-1.105	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
A/D	0.433	ambiguous	0.4529	ambiguous	-1.594	Destabilizing	0.994	D	0.699	prob.neutral	N	0.499788197	None	None	N
A/E	0.3311	likely_benign	0.3273	benign	-1.604	Destabilizing	0.983	D	0.703	prob.neutral	None	None	None	None	N
A/F	0.3435	ambiguous	0.3516	ambiguous	-1.09	Destabilizing	0.999	D	0.758	deleterious	None	None	None	None	N
A/G	0.1475	likely_benign	0.1588	benign	-1.347	Destabilizing	0.948	D	0.612	neutral	N	0.502749863	None	None	N
A/H	0.5128	ambiguous	0.5126	ambiguous	-1.487	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
A/I	0.2743	likely_benign	0.2964	benign	-0.438	Destabilizing	0.998	D	0.753	deleterious	None	None	None	None	N
A/K	0.5391	ambiguous	0.5393	ambiguous	-1.359	Destabilizing	0.983	D	0.717	prob.delet.	None	None	None	None	N
A/L	0.2035	likely_benign	0.2102	benign	-0.438	Destabilizing	0.992	D	0.68	prob.neutral	None	None	None	None	N
A/M	0.2236	likely_benign	0.2303	benign	-0.408	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
A/N	0.2824	likely_benign	0.3053	benign	-1.149	Destabilizing	0.995	D	0.711	prob.delet.	None	None	None	None	N
A/P	0.9312	likely_pathogenic	0.9477	pathogenic	-0.606	Destabilizing	0.997	D	0.755	deleterious	N	0.509161759	None	None	N
A/Q	0.3533	ambiguous	0.3485	ambiguous	-1.305	Destabilizing	0.998	D	0.767	deleterious	None	None	None	None	N
A/R	0.476	ambiguous	0.4555	ambiguous	-0.992	Destabilizing	0.998	D	0.769	deleterious	None	None	None	None	N
A/S	0.0861	likely_benign	0.0889	benign	-1.499	Destabilizing	0.418	N	0.335	neutral	N	0.383684205	None	None	N
A/T	0.0821	likely_benign	0.0862	benign	-1.416	Destabilizing	0.956	D	0.617	neutral	N	0.380304666	None	None	N
A/V	0.1451	likely_benign	0.1528	benign	-0.606	Destabilizing	0.989	D	0.672	neutral	N	0.452411247	None	None	N
A/W	0.7485	likely_pathogenic	0.742	pathogenic	-1.458	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
A/Y	0.4942	ambiguous	0.5186	ambiguous	-1.058	Destabilizing	0.999	D	0.744	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.