TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3171	9736;9737;9738	chr2:178766573;178766572;178766571	chr2:179631300;179631299;179631298
N2AB	3171	9736;9737;9738	chr2:178766573;178766572;178766571	chr2:179631300;179631299;179631298
N2A	3171	9736;9737;9738	chr2:178766573;178766572;178766571	chr2:179631300;179631299;179631298
N2B	3125	9598;9599;9600	chr2:178766573;178766572;178766571	chr2:179631300;179631299;179631298
Novex-1	3125	9598;9599;9600	chr2:178766573;178766572;178766571	chr2:179631300;179631299;179631298
Novex-2	3125	9598;9599;9600	chr2:178766573;178766572;178766571	chr2:179631300;179631299;179631298
Novex-3	3171	9736;9737;9738	chr2:178766573;178766572;178766571	chr2:179631300;179631299;179631298

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-22
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.5962
• 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/I	rs139992576	0.342	1.0	D	0.69	0.592	0.741454687348	gnomAD-2.1.1	1.2E-05	None	None	None	None	N	None	0	0	None	0	0	None	9.8E-05	None	0	0	0
N/I	rs139992576	0.342	1.0	D	0.69	0.592	0.741454687348	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07125E-04	0
N/I	rs139992576	0.342	1.0	D	0.69	0.592	0.741454687348	gnomAD-4.0.0	3.71727E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.58762E-05	0
N/K	None	None	1.0	N	0.649	0.284	0.178374595973	gnomAD-4.0.0	6.84104E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15934E-05	0
N/S	rs139992576	-0.15	0.999	N	0.477	0.316	None	gnomAD-2.1.1	6.78E-05	None	None	None	None	N	None	6.15E-05	0	None	0	0	None	3.27E-05	None	0	1.32535E-04	0
N/S	rs139992576	-0.15	0.999	N	0.477	0.316	None	gnomAD-3.1.2	5.91E-05	None	None	None	None	N	None	7.24E-05	0	0	0	1.92234E-04	None	0	0	5.88E-05	0	4.78011E-04
N/S	rs139992576	-0.15	0.999	N	0.477	0.316	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	1E-03	0	None	None	None	0	None
N/S	rs139992576	-0.15	0.999	N	0.477	0.316	None	gnomAD-4.0.0	8.73559E-05	None	None	None	None	N	None	3.99712E-05	0	None	0	4.45851E-05	None	0	1.65017E-04	1.1017E-04	2.19587E-05	4.79985E-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	0.9151	likely_pathogenic	0.8538	pathogenic	-0.399	Destabilizing	1.0	D	0.625	neutral	None	None	None	None	N
N/C	0.9712	likely_pathogenic	0.9423	pathogenic	0.2	Stabilizing	1.0	D	0.659	neutral	None	None	None	None	N
N/D	0.7606	likely_pathogenic	0.6302	pathogenic	0.163	Stabilizing	0.999	D	0.528	neutral	N	0.508215335	None	None	N
N/E	0.9754	likely_pathogenic	0.9612	pathogenic	0.172	Stabilizing	0.999	D	0.63	neutral	None	None	None	None	N
N/F	0.9884	likely_pathogenic	0.9832	pathogenic	-0.562	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	N
N/G	0.9105	likely_pathogenic	0.8269	pathogenic	-0.631	Destabilizing	0.999	D	0.491	neutral	None	None	None	None	N
N/H	0.8682	likely_pathogenic	0.7854	pathogenic	-0.53	Destabilizing	1.0	D	0.622	neutral	D	0.541988563	None	None	N
N/I	0.9364	likely_pathogenic	0.9203	pathogenic	0.137	Stabilizing	1.0	D	0.69	prob.neutral	D	0.581252046	None	None	N
N/K	0.9894	likely_pathogenic	0.9836	pathogenic	0.026	Stabilizing	1.0	D	0.649	neutral	N	0.497328029	None	None	N
N/L	0.9016	likely_pathogenic	0.8764	pathogenic	0.137	Stabilizing	1.0	D	0.671	neutral	None	None	None	None	N
N/M	0.9368	likely_pathogenic	0.9186	pathogenic	0.341	Stabilizing	1.0	D	0.607	neutral	None	None	None	None	N
N/P	0.9758	likely_pathogenic	0.9593	pathogenic	-0.012	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
N/Q	0.9717	likely_pathogenic	0.9563	pathogenic	-0.463	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
N/R	0.9852	likely_pathogenic	0.9752	pathogenic	0.032	Stabilizing	1.0	D	0.673	neutral	None	None	None	None	N
N/S	0.2478	likely_benign	0.1544	benign	-0.347	Destabilizing	0.999	D	0.477	neutral	N	0.479655817	None	None	N
N/T	0.6092	likely_pathogenic	0.453	ambiguous	-0.171	Destabilizing	0.999	D	0.627	neutral	D	0.534533798	None	None	N
N/V	0.9373	likely_pathogenic	0.9169	pathogenic	-0.012	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
N/W	0.996	likely_pathogenic	0.9927	pathogenic	-0.481	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	N
N/Y	0.9275	likely_pathogenic	0.9003	pathogenic	-0.228	Destabilizing	1.0	D	0.651	neutral	D	0.542163198	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.