TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19042	57349;57350;57351	chr2:178598046;178598045;178598044	chr2:179462773;179462772;179462771
N2AB	17401	52426;52427;52428	chr2:178598046;178598045;178598044	chr2:179462773;179462772;179462771
N2A	16474	49645;49646;49647	chr2:178598046;178598045;178598044	chr2:179462773;179462772;179462771
N2B	9977	30154;30155;30156	chr2:178598046;178598045;178598044	chr2:179462773;179462772;179462771
Novex-1	10102	30529;30530;30531	chr2:178598046;178598045;178598044	chr2:179462773;179462772;179462771
Novex-2	10169	30730;30731;30732	chr2:178598046;178598045;178598044	chr2:179462773;179462772;179462771
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-26
• Domain position: 55
• Structural Position: 75
• Q(SASA): 0.3256
• 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
E/Q	rs1471278707	-0.266	0.928	N	0.526	0.144	0.203808441222	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
E/Q	rs1471278707	-0.266	0.928	N	0.526	0.144	0.203808441222	gnomAD-4.0.0	1.59434E-06	None	None	None	None	N	None	0	2.29158E-05	None	0	0	None	0	0	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
E/A	0.2256	likely_benign	0.1725	benign	-0.709	Destabilizing	0.928	D	0.518	neutral	N	0.442829037	None	None	N
E/C	0.9255	likely_pathogenic	0.8814	pathogenic	-0.34	Destabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	N
E/D	0.254	likely_benign	0.2564	benign	-0.567	Destabilizing	0.928	D	0.39	neutral	N	0.440788809	None	None	N
E/F	0.8534	likely_pathogenic	0.7808	pathogenic	-0.172	Destabilizing	0.999	D	0.732	prob.delet.	None	None	None	None	N
E/G	0.3842	ambiguous	0.3034	benign	-1.001	Destabilizing	0.978	D	0.637	neutral	N	0.437423217	None	None	N
E/H	0.8089	likely_pathogenic	0.7347	pathogenic	-0.155	Destabilizing	0.998	D	0.64	neutral	None	None	None	None	N
E/I	0.368	ambiguous	0.3057	benign	0.066	Stabilizing	0.992	D	0.759	deleterious	None	None	None	None	N
E/K	0.5075	ambiguous	0.4028	ambiguous	-0.052	Destabilizing	0.865	D	0.388	neutral	N	0.43603635	None	None	N
E/L	0.4347	ambiguous	0.35	ambiguous	0.066	Stabilizing	0.983	D	0.706	prob.neutral	None	None	None	None	N
E/M	0.5274	ambiguous	0.4399	ambiguous	0.263	Stabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	N
E/N	0.5064	ambiguous	0.4417	ambiguous	-0.617	Destabilizing	0.983	D	0.614	neutral	None	None	None	None	N
E/P	0.4722	ambiguous	0.3525	ambiguous	-0.172	Destabilizing	0.997	D	0.714	prob.delet.	None	None	None	None	N
E/Q	0.3445	ambiguous	0.2869	benign	-0.509	Destabilizing	0.928	D	0.526	neutral	N	0.472573154	None	None	N
E/R	0.6779	likely_pathogenic	0.5668	pathogenic	0.234	Stabilizing	0.11	N	0.221	neutral	None	None	None	None	N
E/S	0.4545	ambiguous	0.3628	ambiguous	-0.814	Destabilizing	0.944	D	0.535	neutral	None	None	None	None	N
E/T	0.3564	ambiguous	0.2863	benign	-0.563	Destabilizing	0.983	D	0.667	neutral	None	None	None	None	N
E/V	0.2193	likely_benign	0.1819	benign	-0.172	Destabilizing	0.989	D	0.709	prob.delet.	N	0.456662339	None	None	N
E/W	0.9585	likely_pathogenic	0.9372	pathogenic	0.126	Stabilizing	0.999	D	0.732	prob.delet.	None	None	None	None	N
E/Y	0.7612	likely_pathogenic	0.6653	pathogenic	0.095	Stabilizing	0.997	D	0.726	prob.delet.	None	None	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.