TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2732	8419;8420;8421	chr2:178770598;178770597;178770596	chr2:179635325;179635324;179635323
N2AB	2732	8419;8420;8421	chr2:178770598;178770597;178770596	chr2:179635325;179635324;179635323
N2A	2732	8419;8420;8421	chr2:178770598;178770597;178770596	chr2:179635325;179635324;179635323
N2B	2686	8281;8282;8283	chr2:178770598;178770597;178770596	chr2:179635325;179635324;179635323
Novex-1	2686	8281;8282;8283	chr2:178770598;178770597;178770596	chr2:179635325;179635324;179635323
Novex-2	2686	8281;8282;8283	chr2:178770598;178770597;178770596	chr2:179635325;179635324;179635323
Novex-3	2732	8419;8420;8421	chr2:178770598;178770597;178770596	chr2:179635325;179635324;179635323

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-17
• Domain position: 26
• Structural Position: 40
• Q(SASA): 0.5124
• 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
H/Y	None	None	0.997	D	0.49	0.514	0.507987536778	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

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
H/A	0.739	likely_pathogenic	0.8473	pathogenic	0.234	Stabilizing	0.985	D	0.438	neutral	None	None	None	None	N
H/C	0.5738	likely_pathogenic	0.7544	pathogenic	0.587	Stabilizing	1.0	D	0.609	neutral	None	None	None	None	N
H/D	0.6009	likely_pathogenic	0.7579	pathogenic	-0.122	Destabilizing	0.98	D	0.413	neutral	N	0.506529788	None	None	N
H/E	0.7332	likely_pathogenic	0.8739	pathogenic	-0.079	Destabilizing	0.971	D	0.421	neutral	None	None	None	None	N
H/F	0.6301	likely_pathogenic	0.7667	pathogenic	1.062	Stabilizing	0.999	D	0.414	neutral	None	None	None	None	N
H/G	0.8206	likely_pathogenic	0.9127	pathogenic	-0.066	Destabilizing	0.993	D	0.453	neutral	None	None	None	None	N
H/I	0.7141	likely_pathogenic	0.8578	pathogenic	1.012	Stabilizing	0.999	D	0.582	neutral	None	None	None	None	N
H/K	0.6975	likely_pathogenic	0.8718	pathogenic	0.162	Stabilizing	0.971	D	0.419	neutral	None	None	None	None	N
H/L	0.3191	likely_benign	0.4516	ambiguous	1.012	Stabilizing	0.997	D	0.523	neutral	D	0.631553381	None	None	N
H/M	0.8318	likely_pathogenic	0.9106	pathogenic	0.681	Stabilizing	1.0	D	0.519	neutral	None	None	None	None	N
H/N	0.2976	likely_benign	0.4521	ambiguous	0.049	Stabilizing	0.99	D	0.507	neutral	D	0.630883008	None	None	N
H/P	0.623	likely_pathogenic	0.704	pathogenic	0.778	Stabilizing	0.999	D	0.495	neutral	D	0.525613261	None	None	N
H/Q	0.6383	likely_pathogenic	0.8226	pathogenic	0.196	Stabilizing	0.817	D	0.214	neutral	D	0.535853725	None	None	N
H/R	0.439	ambiguous	0.7315	pathogenic	-0.467	Destabilizing	0.98	D	0.434	neutral	N	0.508400091	None	None	N
H/S	0.5721	likely_pathogenic	0.708	pathogenic	0.154	Stabilizing	0.985	D	0.421	neutral	None	None	None	None	N
H/T	0.76	likely_pathogenic	0.8858	pathogenic	0.304	Stabilizing	0.998	D	0.441	neutral	None	None	None	None	N
H/V	0.662	likely_pathogenic	0.8288	pathogenic	0.778	Stabilizing	0.998	D	0.564	neutral	None	None	None	None	N
H/W	0.7144	likely_pathogenic	0.8087	pathogenic	1.096	Stabilizing	1.0	D	0.566	neutral	None	None	None	None	N
H/Y	0.202	likely_benign	0.3202	benign	1.315	Stabilizing	0.997	D	0.49	neutral	D	0.536589501	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.