TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20674	62245;62246;62247	chr2:178589705;178589704;178589703	chr2:179454432;179454431;179454430
N2AB	19033	57322;57323;57324	chr2:178589705;178589704;178589703	chr2:179454432;179454431;179454430
N2A	18106	54541;54542;54543	chr2:178589705;178589704;178589703	chr2:179454432;179454431;179454430
N2B	11609	35050;35051;35052	chr2:178589705;178589704;178589703	chr2:179454432;179454431;179454430
Novex-1	11734	35425;35426;35427	chr2:178589705;178589704;178589703	chr2:179454432;179454431;179454430
Novex-2	11801	35626;35627;35628	chr2:178589705;178589704;178589703	chr2:179454432;179454431;179454430
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-38
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.4481
• 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
N/K	rs1171410396	0.35	1.0	N	0.703	0.347	0.219573609325	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
N/K	rs1171410396	0.35	1.0	N	0.703	0.347	0.219573609325	gnomAD-4.0.0	1.59179E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85945E-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
N/A	0.71	likely_pathogenic	0.6952	pathogenic	-0.453	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
N/C	0.7643	likely_pathogenic	0.7285	pathogenic	0.333	Stabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
N/D	0.4785	ambiguous	0.4234	ambiguous	-0.068	Destabilizing	0.999	D	0.593	neutral	N	0.495762232	None	None	N
N/E	0.842	likely_pathogenic	0.8057	pathogenic	-0.067	Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
N/F	0.8359	likely_pathogenic	0.8244	pathogenic	-0.546	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
N/G	0.718	likely_pathogenic	0.7097	pathogenic	-0.692	Destabilizing	0.999	D	0.564	neutral	None	None	None	None	N
N/H	0.3315	likely_benign	0.3351	benign	-0.696	Destabilizing	1.0	D	0.627	neutral	N	0.478986697	None	None	N
N/I	0.7515	likely_pathogenic	0.7045	pathogenic	0.107	Stabilizing	1.0	D	0.827	deleterious	N	0.482265153	None	None	N
N/K	0.8057	likely_pathogenic	0.7813	pathogenic	-0.199	Destabilizing	1.0	D	0.703	prob.neutral	N	0.48502795	None	None	N
N/L	0.6808	likely_pathogenic	0.6497	pathogenic	0.107	Stabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
N/M	0.7047	likely_pathogenic	0.6882	pathogenic	0.445	Stabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
N/P	0.9836	likely_pathogenic	0.9723	pathogenic	-0.051	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
N/Q	0.7521	likely_pathogenic	0.7398	pathogenic	-0.528	Destabilizing	1.0	D	0.668	neutral	None	None	None	None	N
N/R	0.8474	likely_pathogenic	0.8139	pathogenic	-0.197	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	N
N/S	0.3624	ambiguous	0.3627	ambiguous	-0.372	Destabilizing	0.999	D	0.547	neutral	N	0.505403222	None	None	N
N/T	0.602	likely_pathogenic	0.5714	pathogenic	-0.222	Destabilizing	0.999	D	0.693	prob.neutral	N	0.51742837	None	None	N
N/V	0.7574	likely_pathogenic	0.7187	pathogenic	-0.051	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
N/W	0.9624	likely_pathogenic	0.9552	pathogenic	-0.477	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
N/Y	0.3928	ambiguous	0.3655	ambiguous	-0.266	Destabilizing	1.0	D	0.801	deleterious	N	0.505738232	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.