TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19911	59956;59957;59958	chr2:178592173;178592172;178592171	chr2:179456900;179456899;179456898
N2AB	18270	55033;55034;55035	chr2:178592173;178592172;178592171	chr2:179456900;179456899;179456898
N2A	17343	52252;52253;52254	chr2:178592173;178592172;178592171	chr2:179456900;179456899;179456898
N2B	10846	32761;32762;32763	chr2:178592173;178592172;178592171	chr2:179456900;179456899;179456898
Novex-1	10971	33136;33137;33138	chr2:178592173;178592172;178592171	chr2:179456900;179456899;179456898
Novex-2	11038	33337;33338;33339	chr2:178592173;178592172;178592171	chr2:179456900;179456899;179456898
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-32
• Domain position: 35
• Structural Position: 37
• Q(SASA): 0.1466
• 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/H	None	None	1.0	N	0.675	0.377	0.329282125956	gnomAD-4.0.0	6.84614E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99706E-07	0	0
N/S	None	None	0.999	N	0.538	0.351	0.312608672186	gnomAD-4.0.0	1.36922E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99693E-07	0	1.65815E-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
N/A	0.4934	ambiguous	0.4957	ambiguous	-0.7	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
N/C	0.4309	ambiguous	0.4051	ambiguous	-0.541	Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
N/D	0.3961	ambiguous	0.3989	ambiguous	-2.19	Highly Destabilizing	0.999	D	0.563	neutral	N	0.514382491	None	None	N
N/E	0.8378	likely_pathogenic	0.8523	pathogenic	-2.024	Highly Destabilizing	0.999	D	0.624	neutral	None	None	None	None	N
N/F	0.8449	likely_pathogenic	0.8629	pathogenic	-0.644	Destabilizing	1.0	D	0.929	deleterious	None	None	None	None	N
N/G	0.3565	ambiguous	0.3474	ambiguous	-1.019	Destabilizing	0.999	D	0.545	neutral	None	None	None	None	N
N/H	0.1342	likely_benign	0.1274	benign	-0.784	Destabilizing	1.0	D	0.675	neutral	N	0.449467008	None	None	N
N/I	0.8763	likely_pathogenic	0.9057	pathogenic	0.111	Stabilizing	1.0	D	0.93	deleterious	N	0.474357752	None	None	N
N/K	0.7863	likely_pathogenic	0.8069	pathogenic	-0.245	Destabilizing	1.0	D	0.656	neutral	N	0.498719605	None	None	N
N/L	0.7592	likely_pathogenic	0.7945	pathogenic	0.111	Stabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
N/M	0.8123	likely_pathogenic	0.8383	pathogenic	0.362	Stabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
N/P	0.9921	likely_pathogenic	0.9933	pathogenic	-0.132	Destabilizing	1.0	D	0.92	deleterious	None	None	None	None	N
N/Q	0.652	likely_pathogenic	0.6604	pathogenic	-1.164	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
N/R	0.6932	likely_pathogenic	0.7143	pathogenic	-0.251	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	N
N/S	0.0967	likely_benign	0.0935	benign	-1.084	Destabilizing	0.999	D	0.538	neutral	N	0.44134617	None	None	N
N/T	0.4111	ambiguous	0.4419	ambiguous	-0.76	Destabilizing	0.999	D	0.608	neutral	N	0.514209133	None	None	N
N/V	0.8032	likely_pathogenic	0.8464	pathogenic	-0.132	Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
N/W	0.9296	likely_pathogenic	0.9338	pathogenic	-0.64	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
N/Y	0.4033	ambiguous	0.4237	ambiguous	-0.206	Destabilizing	1.0	D	0.912	deleterious	N	0.468824344	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.