TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34409	103450;103451;103452	chr2:178533390;178533389;178533388	chr2:179398117;179398116;179398115
N2AB	32768	98527;98528;98529	chr2:178533390;178533389;178533388	chr2:179398117;179398116;179398115
N2A	31841	95746;95747;95748	chr2:178533390;178533389;178533388	chr2:179398117;179398116;179398115
N2B	25344	76255;76256;76257	chr2:178533390;178533389;178533388	chr2:179398117;179398116;179398115
Novex-1	25469	76630;76631;76632	chr2:178533390;178533389;178533388	chr2:179398117;179398116;179398115
Novex-2	25536	76831;76832;76833	chr2:178533390;178533389;178533388	chr2:179398117;179398116;179398115
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-162
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.1131
• 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/T	rs879013405	-2.204	0.324	N	0.509	0.335	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
I/T	rs879013405	-2.204	0.324	N	0.509	0.335	None	gnomAD-4.0.0	2.05287E-06	None	None	None	None	N	None	0	2.23614E-05	None	0	0	None	0	0	8.99418E-07	1.15931E-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	0.4926	ambiguous	0.469	ambiguous	-2.358	Highly Destabilizing	0.116	N	0.478	neutral	None	None	None	None	N
I/C	0.761	likely_pathogenic	0.7573	pathogenic	-1.602	Destabilizing	0.944	D	0.547	neutral	None	None	None	None	N
I/D	0.9485	likely_pathogenic	0.9526	pathogenic	-2.236	Highly Destabilizing	0.818	D	0.639	neutral	None	None	None	None	N
I/E	0.8293	likely_pathogenic	0.8395	pathogenic	-2.086	Highly Destabilizing	0.818	D	0.623	neutral	None	None	None	None	N
I/F	0.2983	likely_benign	0.2587	benign	-1.423	Destabilizing	0.001	N	0.375	neutral	N	0.462274094	None	None	N
I/G	0.9028	likely_pathogenic	0.885	pathogenic	-2.845	Highly Destabilizing	0.818	D	0.621	neutral	None	None	None	None	N
I/H	0.7443	likely_pathogenic	0.7575	pathogenic	-2.185	Highly Destabilizing	0.981	D	0.613	neutral	None	None	None	None	N
I/K	0.5977	likely_pathogenic	0.6304	pathogenic	-1.804	Destabilizing	0.818	D	0.624	neutral	None	None	None	None	N
I/L	0.2198	likely_benign	0.1818	benign	-0.995	Destabilizing	0.001	N	0.161	neutral	N	0.487689827	None	None	N
I/M	0.1265	likely_benign	0.1139	benign	-0.872	Destabilizing	0.627	D	0.59	neutral	N	0.51276163	None	None	N
I/N	0.6666	likely_pathogenic	0.6839	pathogenic	-1.888	Destabilizing	0.912	D	0.65	neutral	N	0.507181307	None	None	N
I/P	0.9756	likely_pathogenic	0.9733	pathogenic	-1.425	Destabilizing	0.932	D	0.641	neutral	None	None	None	None	N
I/Q	0.6862	likely_pathogenic	0.7044	pathogenic	-1.871	Destabilizing	0.932	D	0.639	neutral	None	None	None	None	N
I/R	0.4625	ambiguous	0.5294	ambiguous	-1.379	Destabilizing	0.818	D	0.647	neutral	None	None	None	None	N
I/S	0.5782	likely_pathogenic	0.5798	pathogenic	-2.603	Highly Destabilizing	0.324	N	0.553	neutral	N	0.495064533	None	None	N
I/T	0.1742	likely_benign	0.1621	benign	-2.317	Highly Destabilizing	0.324	N	0.509	neutral	N	0.508817247	None	None	N
I/V	0.087	likely_benign	0.0748	benign	-1.425	Destabilizing	0.001	N	0.145	neutral	N	0.453595896	None	None	N
I/W	0.8669	likely_pathogenic	0.8657	pathogenic	-1.707	Destabilizing	0.981	D	0.627	neutral	None	None	None	None	N
I/Y	0.6797	likely_pathogenic	0.682	pathogenic	-1.448	Destabilizing	0.527	D	0.575	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.