TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28165	84718;84719;84720	chr2:178561639;178561638;178561637	chr2:179426366;179426365;179426364
N2AB	26524	79795;79796;79797	chr2:178561639;178561638;178561637	chr2:179426366;179426365;179426364
N2A	25597	77014;77015;77016	chr2:178561639;178561638;178561637	chr2:179426366;179426365;179426364
N2B	19100	57523;57524;57525	chr2:178561639;178561638;178561637	chr2:179426366;179426365;179426364
Novex-1	19225	57898;57899;57900	chr2:178561639;178561638;178561637	chr2:179426366;179426365;179426364
Novex-2	19292	58099;58100;58101	chr2:178561639;178561638;178561637	chr2:179426366;179426365;179426364
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-93
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.6748
• 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
H/D	rs1472903597	-0.128	0.549	N	0.325	0.309	0.141422826196	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	1.14732E-04	0	None	0	0	None	0	None	0	0	0
H/D	rs1472903597	-0.128	0.549	N	0.325	0.309	0.141422826196	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
H/D	rs1472903597	-0.128	0.549	N	0.325	0.309	0.141422826196	gnomAD-4.0.0	1.24146E-06	None	None	None	None	N	None	2.67308E-05	0	None	0	0	None	0	0	0	0	0
H/R	rs876658088	None	0.379	N	0.217	0.161	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
H/R	rs876658088	None	0.379	N	0.217	0.161	None	gnomAD-4.0.0	1.42753E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.95149E-05	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
H/A	0.2038	likely_benign	0.1808	benign	0.193	Stabilizing	0.25	N	0.335	neutral	None	None	None	None	N
H/C	0.1634	likely_benign	0.1456	benign	0.526	Stabilizing	0.992	D	0.418	neutral	None	None	None	None	N
H/D	0.206	likely_benign	0.1796	benign	-0.057	Destabilizing	0.549	D	0.325	neutral	N	0.407289524	None	None	N
H/E	0.2285	likely_benign	0.2083	benign	-0.028	Destabilizing	0.25	N	0.221	neutral	None	None	None	None	N
H/F	0.2174	likely_benign	0.2094	benign	0.913	Stabilizing	0.739	D	0.332	neutral	None	None	None	None	N
H/G	0.2794	likely_benign	0.2359	benign	-0.086	Destabilizing	0.617	D	0.359	neutral	None	None	None	None	N
H/I	0.2454	likely_benign	0.2275	benign	0.905	Stabilizing	0.739	D	0.429	neutral	None	None	None	None	N
H/K	0.2263	likely_benign	0.2079	benign	0.112	Stabilizing	0.005	N	0.132	neutral	None	None	None	None	N
H/L	0.1066	likely_benign	0.0964	benign	0.905	Stabilizing	0.004	N	0.223	neutral	N	0.449312292	None	None	N
H/M	0.3111	likely_benign	0.3009	benign	0.627	Stabilizing	0.85	D	0.405	neutral	None	None	None	None	N
H/N	0.0959	likely_benign	0.0878	benign	0.035	Stabilizing	0.549	D	0.239	neutral	N	0.39203207	None	None	N
H/P	0.5812	likely_pathogenic	0.5126	ambiguous	0.692	Stabilizing	0.896	D	0.395	neutral	N	0.478170975	None	None	N
H/Q	0.1354	likely_benign	0.1238	benign	0.153	Stabilizing	0.016	N	0.162	neutral	N	0.457507701	None	None	N
H/R	0.1181	likely_benign	0.1027	benign	-0.434	Destabilizing	0.379	N	0.217	neutral	N	0.438479223	None	None	N
H/S	0.1606	likely_benign	0.1432	benign	0.107	Stabilizing	0.447	N	0.286	neutral	None	None	None	None	N
H/T	0.1961	likely_benign	0.1779	benign	0.238	Stabilizing	0.617	D	0.402	neutral	None	None	None	None	N
H/V	0.1984	likely_benign	0.1814	benign	0.692	Stabilizing	0.447	N	0.411	neutral	None	None	None	None	N
H/W	0.3359	likely_benign	0.3113	benign	0.926	Stabilizing	0.992	D	0.439	neutral	None	None	None	None	N
H/Y	0.0844	likely_benign	0.0794	benign	1.168	Stabilizing	0.712	D	0.31	neutral	N	0.489985479	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.