TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21530	64813;64814;64815	chr2:178585156;178585155;178585154	chr2:179449883;179449882;179449881
N2AB	19889	59890;59891;59892	chr2:178585156;178585155;178585154	chr2:179449883;179449882;179449881
N2A	18962	57109;57110;57111	chr2:178585156;178585155;178585154	chr2:179449883;179449882;179449881
N2B	12465	37618;37619;37620	chr2:178585156;178585155;178585154	chr2:179449883;179449882;179449881
Novex-1	12590	37993;37994;37995	chr2:178585156;178585155;178585154	chr2:179449883;179449882;179449881
Novex-2	12657	38194;38195;38196	chr2:178585156;178585155;178585154	chr2:179449883;179449882;179449881
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-124
• Domain position: 62
• Structural Position: 145
• Q(SASA): 0.2567
• 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
T/N	None	None	0.188	N	0.402	0.125	0.236890367714	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
T/A	0.084	likely_benign	0.0822	benign	-0.788	Destabilizing	None	N	0.227	neutral	N	0.509315893	None	None	N
T/C	0.2563	likely_benign	0.2443	benign	-0.313	Destabilizing	0.824	D	0.425	neutral	None	None	None	None	N
T/D	0.347	ambiguous	0.3263	benign	-0.615	Destabilizing	0.081	N	0.393	neutral	None	None	None	None	N
T/E	0.2687	likely_benign	0.2684	benign	-0.605	Destabilizing	0.081	N	0.397	neutral	None	None	None	None	N
T/F	0.2352	likely_benign	0.2418	benign	-0.832	Destabilizing	0.38	N	0.497	neutral	None	None	None	None	N
T/G	0.1659	likely_benign	0.1483	benign	-1.07	Destabilizing	0.081	N	0.449	neutral	None	None	None	None	N
T/H	0.2104	likely_benign	0.2174	benign	-1.422	Destabilizing	0.824	D	0.465	neutral	None	None	None	None	N
T/I	0.1787	likely_benign	0.1858	benign	-0.119	Destabilizing	0.188	N	0.398	neutral	D	0.534771698	None	None	N
T/K	0.1638	likely_benign	0.1685	benign	-0.835	Destabilizing	0.002	N	0.288	neutral	None	None	None	None	N
T/L	0.0819	likely_benign	0.083	benign	-0.119	Destabilizing	0.035	N	0.408	neutral	None	None	None	None	N
T/M	0.0851	likely_benign	0.0896	benign	0.353	Stabilizing	0.035	N	0.443	neutral	None	None	None	None	N
T/N	0.0995	likely_benign	0.0999	benign	-0.81	Destabilizing	0.188	N	0.402	neutral	N	0.508238457	None	None	N
T/P	0.3616	ambiguous	0.3604	ambiguous	-0.309	Destabilizing	0.317	N	0.407	neutral	N	0.518586838	None	None	N
T/Q	0.1654	likely_benign	0.1737	benign	-0.957	Destabilizing	0.38	N	0.43	neutral	None	None	None	None	N
T/R	0.166	likely_benign	0.1742	benign	-0.612	Destabilizing	0.235	N	0.394	neutral	None	None	None	None	N
T/S	0.0777	likely_benign	0.0747	benign	-1.019	Destabilizing	None	N	0.303	neutral	N	0.462274094	None	None	N
T/V	0.1243	likely_benign	0.1267	benign	-0.309	Destabilizing	0.081	N	0.366	neutral	None	None	None	None	N
T/W	0.5872	likely_pathogenic	0.5869	pathogenic	-0.824	Destabilizing	0.935	D	0.567	neutral	None	None	None	None	N
T/Y	0.2895	likely_benign	0.2767	benign	-0.589	Destabilizing	0.555	D	0.491	neutral	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.