TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35609	107050;107051;107052	chr2:178528926;178528925;178528924	chr2:179393653;179393652;179393651
N2AB	33968	102127;102128;102129	chr2:178528926;178528925;178528924	chr2:179393653;179393652;179393651
N2A	33041	99346;99347;99348	chr2:178528926;178528925;178528924	chr2:179393653;179393652;179393651
N2B	26544	79855;79856;79857	chr2:178528926;178528925;178528924	chr2:179393653;179393652;179393651
Novex-1	26669	80230;80231;80232	chr2:178528926;178528925;178528924	chr2:179393653;179393652;179393651
Novex-2	26736	80431;80432;80433	chr2:178528926;178528925;178528924	chr2:179393653;179393652;179393651
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-167
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.0696
• 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
I/M	rs727504540	-0.777	0.901	N	0.701	0.23	0.414539908741	gnomAD-2.1.1	3.03063E-04	None	None	None	None	N	None	0	2.34742E-03	None	0	0	None	0	None	0	7.8E-06	1.40174E-04
I/M	rs727504540	-0.777	0.901	N	0.701	0.23	0.414539908741	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	2.6178E-04	0	0	0	None	0	0	0	0	0
I/M	rs727504540	-0.777	0.901	N	0.701	0.23	0.414539908741	gnomAD-4.0.0	6.56804E-05	None	None	None	None	N	None	8.0079E-05	1.54995E-03	None	0	0	None	0	3.28731E-04	8.4754E-07	0	6.40348E-05
I/N	None	None	0.983	N	0.864	0.658	0.857379640909	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
I/V	rs573508906	-1.223	0.003	N	0.247	0.171	0.471211772063	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
I/V	rs573508906	-1.223	0.003	N	0.247	0.171	0.471211772063	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.06868E-04	0
I/V	rs573508906	-1.223	0.003	N	0.247	0.171	0.471211772063	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	1E-03	None
I/V	rs573508906	-1.223	0.003	N	0.247	0.171	0.471211772063	gnomAD-4.0.0	2.0295E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.69704E-05	3.39997E-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
I/A	0.7753	likely_pathogenic	0.7522	pathogenic	-1.105	Destabilizing	0.415	N	0.758	deleterious	None	None	None	None	N
I/C	0.9373	likely_pathogenic	0.9336	pathogenic	-0.61	Destabilizing	0.989	D	0.78	deleterious	None	None	None	None	N
I/D	0.9106	likely_pathogenic	0.91	pathogenic	-0.66	Destabilizing	0.987	D	0.871	deleterious	None	None	None	None	N
I/E	0.7907	likely_pathogenic	0.7952	pathogenic	-0.725	Destabilizing	0.961	D	0.857	deleterious	None	None	None	None	N
I/F	0.3339	likely_benign	0.3152	benign	-0.892	Destabilizing	0.901	D	0.738	prob.delet.	N	0.480240993	None	None	N
I/G	0.8947	likely_pathogenic	0.8859	pathogenic	-1.34	Destabilizing	0.961	D	0.852	deleterious	None	None	None	None	N
I/H	0.8665	likely_pathogenic	0.866	pathogenic	-0.625	Destabilizing	0.996	D	0.869	deleterious	None	None	None	None	N
I/K	0.6558	likely_pathogenic	0.6727	pathogenic	-0.758	Destabilizing	0.961	D	0.858	deleterious	None	None	None	None	N
I/L	0.2689	likely_benign	0.2491	benign	-0.574	Destabilizing	0.19	N	0.421	neutral	N	0.486135176	None	None	N
I/M	0.1534	likely_benign	0.144	benign	-0.449	Destabilizing	0.901	D	0.701	prob.neutral	N	0.487868759	None	None	N
I/N	0.5466	ambiguous	0.5357	ambiguous	-0.429	Destabilizing	0.983	D	0.864	deleterious	N	0.488735551	None	None	N
I/P	0.9172	likely_pathogenic	0.9117	pathogenic	-0.718	Destabilizing	0.987	D	0.873	deleterious	None	None	None	None	N
I/Q	0.7524	likely_pathogenic	0.7487	pathogenic	-0.672	Destabilizing	0.987	D	0.868	deleterious	None	None	None	None	N
I/R	0.63	likely_pathogenic	0.6393	pathogenic	-0.142	Destabilizing	0.961	D	0.861	deleterious	None	None	None	None	N
I/S	0.6943	likely_pathogenic	0.6741	pathogenic	-0.912	Destabilizing	0.901	D	0.813	deleterious	N	0.488562192	None	None	N
I/T	0.6971	likely_pathogenic	0.6793	pathogenic	-0.871	Destabilizing	0.722	D	0.774	deleterious	N	0.488388834	None	None	N
I/V	0.1816	likely_benign	0.1668	benign	-0.718	Destabilizing	0.003	N	0.247	neutral	N	0.485615101	None	None	N
I/W	0.8852	likely_pathogenic	0.8793	pathogenic	-0.914	Destabilizing	0.996	D	0.862	deleterious	None	None	None	None	N
I/Y	0.7157	likely_pathogenic	0.7055	pathogenic	-0.703	Destabilizing	0.961	D	0.791	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.