TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29296	88111;88112;88113	chr2:178557376;178557375;178557374	chr2:179422103;179422102;179422101
N2AB	27655	83188;83189;83190	chr2:178557376;178557375;178557374	chr2:179422103;179422102;179422101
N2A	26728	80407;80408;80409	chr2:178557376;178557375;178557374	chr2:179422103;179422102;179422101
N2B	20231	60916;60917;60918	chr2:178557376;178557375;178557374	chr2:179422103;179422102;179422101
Novex-1	20356	61291;61292;61293	chr2:178557376;178557375;178557374	chr2:179422103;179422102;179422101
Novex-2	20423	61492;61493;61494	chr2:178557376;178557375;178557374	chr2:179422103;179422102;179422101
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Fn3-101
• Domain position: 60
• Structural Position: 90
• Q(SASA): 0.5368
• 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
H/D	rs1304860683	None	1.0	N	0.726	0.45	0.353336612579	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
H/D	rs1304860683	None	1.0	N	0.726	0.45	0.353336612579	gnomAD-4.0.0	3.09821E-06	None	None	None	None	I	None	1.33451E-05	0	None	0	0	None	0	0	3.3902E-06	0	0
H/Y	None	None	0.999	N	0.534	0.467	0.371903410333	gnomAD-4.0.0	6.84157E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99418E-07	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
H/A	0.3314	likely_benign	0.3012	benign	-0.375	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	I
H/C	0.1986	likely_benign	0.2084	benign	0.286	Stabilizing	1.0	D	0.77	deleterious	None	None	None	None	I
H/D	0.3743	ambiguous	0.3357	benign	-0.382	Destabilizing	1.0	D	0.726	prob.delet.	N	0.504530857	None	None	I
H/E	0.449	ambiguous	0.3792	ambiguous	-0.296	Destabilizing	0.999	D	0.529	neutral	None	None	None	None	I
H/F	0.3647	ambiguous	0.3262	benign	0.788	Stabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
H/G	0.4511	ambiguous	0.433	ambiguous	-0.729	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	I
H/I	0.3557	ambiguous	0.3285	benign	0.586	Stabilizing	1.0	D	0.772	deleterious	None	None	None	None	I
H/K	0.4457	ambiguous	0.3919	ambiguous	-0.222	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
H/L	0.1668	likely_benign	0.1577	benign	0.586	Stabilizing	1.0	D	0.73	prob.delet.	N	0.489446761	None	None	I
H/M	0.4915	ambiguous	0.4601	ambiguous	0.342	Stabilizing	1.0	D	0.754	deleterious	None	None	None	None	I
H/N	0.1143	likely_benign	0.1049	benign	-0.428	Destabilizing	0.999	D	0.509	neutral	N	0.458950496	None	None	I
H/P	0.7551	likely_pathogenic	0.766	pathogenic	0.288	Stabilizing	1.0	D	0.751	deleterious	N	0.485771737	None	None	I
H/Q	0.2357	likely_benign	0.2018	benign	-0.216	Destabilizing	1.0	D	0.644	neutral	N	0.404636008	None	None	I
H/R	0.1966	likely_benign	0.1722	benign	-0.774	Destabilizing	1.0	D	0.639	neutral	N	0.407270882	None	None	I
H/S	0.2231	likely_benign	0.2069	benign	-0.386	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	I
H/T	0.2738	likely_benign	0.2476	benign	-0.187	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
H/V	0.2885	likely_benign	0.2685	benign	0.288	Stabilizing	1.0	D	0.76	deleterious	None	None	None	None	I
H/W	0.462	ambiguous	0.4567	ambiguous	1.027	Stabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
H/Y	0.1219	likely_benign	0.113	benign	1.123	Stabilizing	0.999	D	0.534	neutral	N	0.468975488	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.