TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18154	54685;54686;54687	chr2:178604227;178604226;178604225	chr2:179468954;179468953;179468952
N2AB	16513	49762;49763;49764	chr2:178604227;178604226;178604225	chr2:179468954;179468953;179468952
N2A	15586	46981;46982;46983	chr2:178604227;178604226;178604225	chr2:179468954;179468953;179468952
N2B	9089	27490;27491;27492	chr2:178604227;178604226;178604225	chr2:179468954;179468953;179468952
Novex-1	9214	27865;27866;27867	chr2:178604227;178604226;178604225	chr2:179468954;179468953;179468952
Novex-2	9281	28066;28067;28068	chr2:178604227;178604226;178604225	chr2:179468954;179468953;179468952
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-19
• Domain position: 90
• Structural Position: 122
• Q(SASA): 0.6181
• 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/E	None	None	None	N	0.17	0.135	0.21737058555	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
K/A	0.2831	likely_benign	0.2206	benign	-0.66	Destabilizing	0.001	N	0.263	neutral	None	None	None	None	N
K/C	0.4948	ambiguous	0.4156	ambiguous	-0.596	Destabilizing	0.878	D	0.529	neutral	None	None	None	None	N
K/D	0.6531	likely_pathogenic	0.5736	pathogenic	-0.002	Destabilizing	0.064	N	0.377	neutral	None	None	None	None	N
K/E	0.218	likely_benign	0.1734	benign	0.118	Stabilizing	None	N	0.17	neutral	N	0.332264196	None	None	N
K/F	0.5773	likely_pathogenic	0.4822	ambiguous	-0.289	Destabilizing	0.538	D	0.637	neutral	None	None	None	None	N
K/G	0.4733	ambiguous	0.3829	ambiguous	-1.026	Destabilizing	0.121	N	0.388	neutral	None	None	None	None	N
K/H	0.2582	likely_benign	0.2385	benign	-1.219	Destabilizing	0.703	D	0.503	neutral	None	None	None	None	N
K/I	0.1941	likely_benign	0.141	benign	0.291	Stabilizing	0.112	N	0.595	neutral	N	0.453710539	None	None	N
K/L	0.2341	likely_benign	0.1581	benign	0.291	Stabilizing	None	N	0.361	neutral	None	None	None	None	N
K/M	0.1959	likely_benign	0.147	benign	0.1	Stabilizing	0.538	D	0.508	neutral	None	None	None	None	N
K/N	0.427	ambiguous	0.3454	ambiguous	-0.444	Destabilizing	0.001	N	0.187	neutral	N	0.449611441	None	None	N
K/P	0.5705	likely_pathogenic	0.4782	ambiguous	0.004	Stabilizing	0.403	N	0.549	neutral	None	None	None	None	N
K/Q	0.1364	likely_benign	0.1204	benign	-0.474	Destabilizing	0.201	N	0.394	neutral	N	0.419461893	None	None	N
K/R	0.0852	likely_benign	0.0795	benign	-0.548	Destabilizing	0.094	N	0.398	neutral	N	0.453017106	None	None	N
K/S	0.3828	ambiguous	0.3059	benign	-1.129	Destabilizing	0.029	N	0.341	neutral	None	None	None	None	N
K/T	0.1423	likely_benign	0.1141	benign	-0.796	Destabilizing	None	N	0.265	neutral	N	0.420712686	None	None	N
K/V	0.1913	likely_benign	0.1413	benign	0.004	Stabilizing	0.064	N	0.375	neutral	None	None	None	None	N
K/W	0.657	likely_pathogenic	0.6132	pathogenic	-0.151	Destabilizing	0.964	D	0.54	neutral	None	None	None	None	N
K/Y	0.5121	ambiguous	0.4424	ambiguous	0.109	Stabilizing	0.703	D	0.659	prob.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.