TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15663	47212;47213;47214	chr2:178618471;178618470;178618469	chr2:179483198;179483197;179483196
N2AB	14022	42289;42290;42291	chr2:178618471;178618470;178618469	chr2:179483198;179483197;179483196
N2A	13095	39508;39509;39510	chr2:178618471;178618470;178618469	chr2:179483198;179483197;179483196
N2B	6598	20017;20018;20019	chr2:178618471;178618470;178618469	chr2:179483198;179483197;179483196
Novex-1	6723	20392;20393;20394	chr2:178618471;178618470;178618469	chr2:179483198;179483197;179483196
Novex-2	6790	20593;20594;20595	chr2:178618471;178618470;178618469	chr2:179483198;179483197;179483196
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: Fn3-1
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.5208
• 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/D	rs1372948861	0.293	0.117	N	0.267	0.242	0.223847106136	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	9.99E-05	0	None	0	None	0	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	0.3696	ambiguous	0.4401	ambiguous	-0.4	Destabilizing	0.983	D	0.621	neutral	None	None	None	None	N
N/C	0.3993	ambiguous	0.4942	ambiguous	0.224	Stabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
N/D	0.1805	likely_benign	0.206	benign	0.042	Stabilizing	0.117	N	0.267	neutral	N	0.490771154	None	None	N
N/E	0.4567	ambiguous	0.499	ambiguous	0.038	Stabilizing	0.966	D	0.459	neutral	None	None	None	None	N
N/F	0.5705	likely_pathogenic	0.6816	pathogenic	-0.557	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
N/G	0.3213	likely_benign	0.3753	ambiguous	-0.623	Destabilizing	0.983	D	0.413	neutral	None	None	None	None	N
N/H	0.1279	likely_benign	0.1554	benign	-0.552	Destabilizing	0.999	D	0.632	neutral	D	0.547262108	None	None	N
N/I	0.536	ambiguous	0.6255	pathogenic	0.113	Stabilizing	0.997	D	0.775	deleterious	D	0.574122877	None	None	N
N/K	0.3246	likely_benign	0.3853	ambiguous	-0.07	Destabilizing	0.977	D	0.579	neutral	N	0.485665491	None	None	N
N/L	0.4597	ambiguous	0.5535	ambiguous	0.113	Stabilizing	0.998	D	0.752	deleterious	None	None	None	None	N
N/M	0.5102	ambiguous	0.6163	pathogenic	0.377	Stabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
N/P	0.941	likely_pathogenic	0.926	pathogenic	-0.029	Destabilizing	0.998	D	0.746	deleterious	None	None	None	None	N
N/Q	0.3561	ambiguous	0.417	ambiguous	-0.53	Destabilizing	0.998	D	0.658	neutral	None	None	None	None	N
N/R	0.3696	ambiguous	0.4277	ambiguous	-0.026	Destabilizing	0.998	D	0.656	neutral	None	None	None	None	N
N/S	0.1427	likely_benign	0.1688	benign	-0.364	Destabilizing	0.977	D	0.416	neutral	N	0.486675249	None	None	N
N/T	0.2972	likely_benign	0.3549	ambiguous	-0.214	Destabilizing	0.989	D	0.557	neutral	N	0.519999407	None	None	N
N/V	0.5169	ambiguous	0.6081	pathogenic	-0.029	Destabilizing	0.998	D	0.758	deleterious	None	None	None	None	N
N/W	0.811	likely_pathogenic	0.8615	pathogenic	-0.479	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
N/Y	0.2125	likely_benign	0.2737	benign	-0.247	Destabilizing	0.999	D	0.749	deleterious	D	0.685388713	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.