TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33424	100495;100496;100497	chr2:178536477;178536476;178536475	chr2:179401204;179401203;179401202
N2AB	31783	95572;95573;95574	chr2:178536477;178536476;178536475	chr2:179401204;179401203;179401202
N2A	30856	92791;92792;92793	chr2:178536477;178536476;178536475	chr2:179401204;179401203;179401202
N2B	24359	73300;73301;73302	chr2:178536477;178536476;178536475	chr2:179401204;179401203;179401202
Novex-1	24484	73675;73676;73677	chr2:178536477;178536476;178536475	chr2:179401204;179401203;179401202
Novex-2	24551	73876;73877;73878	chr2:178536477;178536476;178536475	chr2:179401204;179401203;179401202
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: Fn3-131
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.2016
• Predicted PPI site: I

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/F	rs1264517895	-1.746	1.0	D	0.835	0.543	0.564835144235	gnomAD-2.1.1	4.41E-06	None	None	None	None	I	None	0	0	None	0	0	None	4.07E-05	None	0	0	0
I/F	rs1264517895	-1.746	1.0	D	0.835	0.543	0.564835144235	gnomAD-4.0.0	5.58079E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	9.914E-05	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
I/A	0.969	likely_pathogenic	0.9766	pathogenic	-2.253	Highly Destabilizing	0.999	D	0.68	prob.neutral	None	None	None	None	I
I/C	0.9729	likely_pathogenic	0.9781	pathogenic	-1.2	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
I/D	0.9955	likely_pathogenic	0.9977	pathogenic	-2.105	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	I
I/E	0.9849	likely_pathogenic	0.9922	pathogenic	-2.037	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
I/F	0.8112	likely_pathogenic	0.876	pathogenic	-1.555	Destabilizing	1.0	D	0.835	deleterious	D	0.541653573	None	None	I
I/G	0.9906	likely_pathogenic	0.9942	pathogenic	-2.653	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
I/H	0.9883	likely_pathogenic	0.9933	pathogenic	-1.932	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
I/K	0.9765	likely_pathogenic	0.9872	pathogenic	-1.703	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	I
I/L	0.476	ambiguous	0.5146	ambiguous	-1.17	Destabilizing	0.993	D	0.433	neutral	N	0.487492165	None	None	I
I/M	0.4818	ambiguous	0.5325	ambiguous	-0.75	Destabilizing	1.0	D	0.804	deleterious	D	0.532832163	None	None	I
I/N	0.852	likely_pathogenic	0.8922	pathogenic	-1.589	Destabilizing	1.0	D	0.855	deleterious	D	0.522325231	None	None	I
I/P	0.9475	likely_pathogenic	0.9605	pathogenic	-1.505	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	I
I/Q	0.9774	likely_pathogenic	0.9875	pathogenic	-1.71	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	I
I/R	0.9713	likely_pathogenic	0.9836	pathogenic	-1.082	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	I
I/S	0.953	likely_pathogenic	0.9691	pathogenic	-2.194	Highly Destabilizing	1.0	D	0.854	deleterious	N	0.521564763	None	None	I
I/T	0.9374	likely_pathogenic	0.9486	pathogenic	-2.009	Highly Destabilizing	1.0	D	0.829	deleterious	N	0.521564763	None	None	I
I/V	0.2357	likely_benign	0.2118	benign	-1.505	Destabilizing	0.993	D	0.414	neutral	N	0.501514768	None	None	I
I/W	0.9925	likely_pathogenic	0.9957	pathogenic	-1.761	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
I/Y	0.957	likely_pathogenic	0.9773	pathogenic	-1.549	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I

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.