TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20329	61210;61211;61212	chr2:178590740;178590739;178590738	chr2:179455467;179455466;179455465
N2AB	18688	56287;56288;56289	chr2:178590740;178590739;178590738	chr2:179455467;179455466;179455465
N2A	17761	53506;53507;53508	chr2:178590740;178590739;178590738	chr2:179455467;179455466;179455465
N2B	11264	34015;34016;34017	chr2:178590740;178590739;178590738	chr2:179455467;179455466;179455465
Novex-1	11389	34390;34391;34392	chr2:178590740;178590739;178590738	chr2:179455467;179455466;179455465
Novex-2	11456	34591;34592;34593	chr2:178590740;178590739;178590738	chr2:179455467;179455466;179455465
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-35
• Domain position: 59
• Structural Position: 90
• Q(SASA): 0.5529
• 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
K/N	None	None	0.722	N	0.577	0.175	0.199424873507	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
K/A	0.4165	ambiguous	0.4218	ambiguous	-0.263	Destabilizing	0.775	D	0.6	neutral	None	None	None	None	N
K/C	0.4877	ambiguous	0.5349	ambiguous	-0.445	Destabilizing	0.996	D	0.746	deleterious	None	None	None	None	N
K/D	0.733	likely_pathogenic	0.7002	pathogenic	0.121	Stabilizing	0.961	D	0.675	prob.neutral	None	None	None	None	N
K/E	0.319	likely_benign	0.2844	benign	0.21	Stabilizing	0.722	D	0.575	neutral	N	0.391341424	None	None	N
K/F	0.758	likely_pathogenic	0.7658	pathogenic	-0.075	Destabilizing	0.987	D	0.738	prob.delet.	None	None	None	None	N
K/G	0.5652	likely_pathogenic	0.5809	pathogenic	-0.578	Destabilizing	0.775	D	0.615	neutral	None	None	None	None	N
K/H	0.2041	likely_benign	0.2152	benign	-0.783	Destabilizing	0.961	D	0.733	prob.delet.	None	None	None	None	N
K/I	0.3895	ambiguous	0.3666	ambiguous	0.527	Stabilizing	0.961	D	0.741	deleterious	None	None	None	None	N
K/L	0.3854	ambiguous	0.3849	ambiguous	0.527	Stabilizing	0.775	D	0.615	neutral	None	None	None	None	N
K/M	0.2546	likely_benign	0.2501	benign	0.154	Stabilizing	0.995	D	0.719	prob.delet.	N	0.458433208	None	None	N
K/N	0.4755	ambiguous	0.443	ambiguous	-0.208	Destabilizing	0.722	D	0.577	neutral	N	0.447157421	None	None	N
K/P	0.9223	likely_pathogenic	0.9135	pathogenic	0.294	Stabilizing	0.987	D	0.717	prob.delet.	None	None	None	None	N
K/Q	0.1206	likely_benign	0.1208	benign	-0.239	Destabilizing	0.722	D	0.603	neutral	N	0.426608791	None	None	N
K/R	0.0695	likely_benign	0.073	benign	-0.314	Destabilizing	0.003	N	0.237	neutral	N	0.372678305	None	None	N
K/S	0.4233	ambiguous	0.4072	ambiguous	-0.777	Destabilizing	0.775	D	0.525	neutral	None	None	None	None	N
K/T	0.1499	likely_benign	0.1399	benign	-0.495	Destabilizing	0.722	D	0.637	neutral	N	0.393629581	None	None	N
K/V	0.3379	likely_benign	0.3289	benign	0.294	Stabilizing	0.961	D	0.655	neutral	None	None	None	None	N
K/W	0.714	likely_pathogenic	0.7465	pathogenic	-0.033	Destabilizing	0.996	D	0.713	prob.delet.	None	None	None	None	N
K/Y	0.5787	likely_pathogenic	0.5925	pathogenic	0.274	Stabilizing	0.987	D	0.743	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.