TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16867	50824;50825;50826	chr2:178611630;178611629;178611628	chr2:179476357;179476356;179476355
N2AB	15226	45901;45902;45903	chr2:178611630;178611629;178611628	chr2:179476357;179476356;179476355
N2A	14299	43120;43121;43122	chr2:178611630;178611629;178611628	chr2:179476357;179476356;179476355
N2B	7802	23629;23630;23631	chr2:178611630;178611629;178611628	chr2:179476357;179476356;179476355
Novex-1	7927	24004;24005;24006	chr2:178611630;178611629;178611628	chr2:179476357;179476356;179476355
Novex-2	7994	24205;24206;24207	chr2:178611630;178611629;178611628	chr2:179476357;179476356;179476355
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: Fn3-11
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.4475
• 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	0.201	N	0.365	0.131	0.183819452728	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
K/R	rs1206991896	-0.592	0.549	N	0.341	0.141	0.165133752707	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
K/R	rs1206991896	-0.592	0.549	N	0.341	0.141	0.165133752707	gnomAD-4.0.0	7.52944E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99747E-06	0	1.65788E-05

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	0.4487	ambiguous	0.5071	ambiguous	-0.135	Destabilizing	0.25	N	0.331	neutral	None	None	None	None	N
K/C	0.8235	likely_pathogenic	0.8422	pathogenic	-0.163	Destabilizing	0.992	D	0.329	neutral	None	None	None	None	N
K/D	0.389	ambiguous	0.4757	ambiguous	0.02	Stabilizing	0.002	N	0.115	neutral	None	None	None	None	N
K/E	0.1856	likely_benign	0.2249	benign	0.082	Stabilizing	0.201	N	0.365	neutral	N	0.395035354	None	None	N
K/F	0.89	likely_pathogenic	0.9101	pathogenic	0.038	Stabilizing	0.972	D	0.336	neutral	None	None	None	None	N
K/G	0.3753	ambiguous	0.4489	ambiguous	-0.43	Destabilizing	0.25	N	0.3	neutral	None	None	None	None	N
K/H	0.3613	ambiguous	0.4002	ambiguous	-0.687	Destabilizing	0.85	D	0.383	neutral	None	None	None	None	N
K/I	0.6561	likely_pathogenic	0.6721	pathogenic	0.597	Stabilizing	0.896	D	0.373	neutral	N	0.472589973	None	None	N
K/L	0.5293	ambiguous	0.5679	pathogenic	0.597	Stabilizing	0.617	D	0.404	neutral	None	None	None	None	N
K/M	0.3833	ambiguous	0.411	ambiguous	0.27	Stabilizing	0.992	D	0.377	neutral	None	None	None	None	N
K/N	0.271	likely_benign	0.3345	benign	0.046	Stabilizing	0.002	N	0.066	neutral	N	0.396457874	None	None	N
K/P	0.841	likely_pathogenic	0.8406	pathogenic	0.383	Stabilizing	0.92	D	0.421	neutral	None	None	None	None	N
K/Q	0.1461	likely_benign	0.1603	benign	-0.036	Destabilizing	0.549	D	0.386	neutral	N	0.434761788	None	None	N
K/R	0.1098	likely_benign	0.1113	benign	-0.282	Destabilizing	0.549	D	0.341	neutral	N	0.421501387	None	None	N
K/S	0.341	ambiguous	0.41	ambiguous	-0.449	Destabilizing	0.021	N	0.099	neutral	None	None	None	None	N
K/T	0.2045	likely_benign	0.2395	benign	-0.214	Destabilizing	0.379	N	0.329	neutral	N	0.343320686	None	None	N
K/V	0.5968	likely_pathogenic	0.622	pathogenic	0.383	Stabilizing	0.617	D	0.371	neutral	None	None	None	None	N
K/W	0.8845	likely_pathogenic	0.8934	pathogenic	0.061	Stabilizing	0.992	D	0.489	neutral	None	None	None	None	N
K/Y	0.7401	likely_pathogenic	0.7769	pathogenic	0.346	Stabilizing	0.972	D	0.345	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.