TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31505	94738;94739;94740	chr2:178547012;178547011;178547010	chr2:179411739;179411738;179411737
N2AB	29864	89815;89816;89817	chr2:178547012;178547011;178547010	chr2:179411739;179411738;179411737
N2A	28937	87034;87035;87036	chr2:178547012;178547011;178547010	chr2:179411739;179411738;179411737
N2B	22440	67543;67544;67545	chr2:178547012;178547011;178547010	chr2:179411739;179411738;179411737
Novex-1	22565	67918;67919;67920	chr2:178547012;178547011;178547010	chr2:179411739;179411738;179411737
Novex-2	22632	68119;68120;68121	chr2:178547012;178547011;178547010	chr2:179411739;179411738;179411737
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: Fn3-117
• Domain position: 98
• Structural Position: 132
• Q(SASA): 0.8468
• Predicted PPI site: I

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/T	rs755756435	0.437	0.997	N	0.723	0.285	0.380564188046	gnomAD-2.1.1	1.22E-05	None	None	None	None	I	None	0	0	None	0	0	None	9.94E-05	None	0	0	0
N/T	rs755756435	0.437	0.997	N	0.723	0.285	0.380564188046	gnomAD-4.0.0	3.43351E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	5.82099E-05	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	0.6096	likely_pathogenic	0.6475	pathogenic	-0.282	Destabilizing	0.999	D	0.605	neutral	None	None	None	None	I
N/C	0.6587	likely_pathogenic	0.6948	pathogenic	0.357	Stabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
N/D	0.257	likely_benign	0.3165	benign	0.033	Stabilizing	0.997	D	0.645	neutral	N	0.359757441	None	None	I
N/E	0.7724	likely_pathogenic	0.8365	pathogenic	-0.016	Destabilizing	0.998	D	0.729	deleterious	None	None	None	None	I
N/F	0.8214	likely_pathogenic	0.8457	pathogenic	-0.734	Destabilizing	1.0	D	0.739	deleterious	None	None	None	None	I
N/G	0.6743	likely_pathogenic	0.7133	pathogenic	-0.43	Destabilizing	0.998	D	0.545	neutral	None	None	None	None	I
N/H	0.2705	likely_benign	0.3049	benign	-0.505	Destabilizing	0.999	D	0.795	deleterious	D	0.531784534	None	None	I
N/I	0.5142	ambiguous	0.5999	pathogenic	0.015	Stabilizing	0.999	D	0.739	deleterious	N	0.521183538	None	None	I
N/K	0.7673	likely_pathogenic	0.8539	pathogenic	0.118	Stabilizing	0.999	D	0.741	deleterious	N	0.50605937	None	None	I
N/L	0.4792	ambiguous	0.5356	ambiguous	0.015	Stabilizing	0.999	D	0.687	prob.delet.	None	None	None	None	I
N/M	0.6047	likely_pathogenic	0.6642	pathogenic	0.372	Stabilizing	1.0	D	0.794	deleterious	None	None	None	None	I
N/P	0.8732	likely_pathogenic	0.8627	pathogenic	-0.059	Destabilizing	0.999	D	0.729	deleterious	None	None	None	None	I
N/Q	0.6925	likely_pathogenic	0.7635	pathogenic	-0.341	Destabilizing	0.999	D	0.778	deleterious	None	None	None	None	I
N/R	0.8356	likely_pathogenic	0.8934	pathogenic	0.184	Stabilizing	0.999	D	0.791	deleterious	None	None	None	None	I
N/S	0.1876	likely_benign	0.2027	benign	-0.071	Destabilizing	0.997	D	0.555	neutral	N	0.466924979	None	None	I
N/T	0.3732	ambiguous	0.4358	ambiguous	0.012	Stabilizing	0.997	D	0.723	deleterious	N	0.465751543	None	None	I
N/V	0.5597	ambiguous	0.631	pathogenic	-0.059	Destabilizing	0.999	D	0.693	prob.delet.	None	None	None	None	I
N/W	0.9429	likely_pathogenic	0.9559	pathogenic	-0.754	Destabilizing	1.0	D	0.739	deleterious	None	None	None	None	I
N/Y	0.333	likely_benign	0.3823	ambiguous	-0.474	Destabilizing	1.0	D	0.751	deleterious	N	0.49990579	None	None	I

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.