TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17533	52822;52823;52824	chr2:178608286;178608285;178608284	chr2:179473013;179473012;179473011
N2AB	15892	47899;47900;47901	chr2:178608286;178608285;178608284	chr2:179473013;179473012;179473011
N2A	14965	45118;45119;45120	chr2:178608286;178608285;178608284	chr2:179473013;179473012;179473011
N2B	8468	25627;25628;25629	chr2:178608286;178608285;178608284	chr2:179473013;179473012;179473011
Novex-1	8593	26002;26003;26004	chr2:178608286;178608285;178608284	chr2:179473013;179473012;179473011
Novex-2	8660	26203;26204;26205	chr2:178608286;178608285;178608284	chr2:179473013;179473012;179473011
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-15
• Domain position: 64
• Structural Position: 96
• Q(SASA): 0.4659
• 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
G/C	rs2055410849	None	1.0	D	0.722	0.66	0.723393103801	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
G/C	rs2055410849	None	1.0	D	0.722	0.66	0.723393103801	gnomAD-4.0.0	6.58111E-06	None	None	None	None	N	None	2.41546E-05	0	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
G/A	0.3344	likely_benign	0.324	benign	-0.335	Destabilizing	1.0	D	0.679	prob.neutral	N	0.508206994	None	None	N
G/C	0.3646	ambiguous	0.345	ambiguous	-0.866	Destabilizing	1.0	D	0.722	prob.delet.	D	0.538935002	None	None	N
G/D	0.3763	ambiguous	0.3549	ambiguous	-0.419	Destabilizing	1.0	D	0.75	deleterious	N	0.491489775	None	None	N
G/E	0.5226	ambiguous	0.5094	ambiguous	-0.552	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
G/F	0.786	likely_pathogenic	0.7887	pathogenic	-0.927	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
G/H	0.6071	likely_pathogenic	0.5554	ambiguous	-0.601	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
G/I	0.6727	likely_pathogenic	0.6747	pathogenic	-0.322	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
G/K	0.7706	likely_pathogenic	0.7012	pathogenic	-0.829	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
G/L	0.7557	likely_pathogenic	0.7479	pathogenic	-0.322	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
G/M	0.7282	likely_pathogenic	0.7049	pathogenic	-0.429	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
G/N	0.3325	likely_benign	0.3071	benign	-0.477	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
G/P	0.9664	likely_pathogenic	0.9684	pathogenic	-0.29	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
G/Q	0.5978	likely_pathogenic	0.5609	ambiguous	-0.71	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
G/R	0.6543	likely_pathogenic	0.5948	pathogenic	-0.423	Destabilizing	1.0	D	0.763	deleterious	N	0.481962438	None	None	N
G/S	0.1658	likely_benign	0.1637	benign	-0.694	Destabilizing	1.0	D	0.754	deleterious	N	0.479947748	None	None	N
G/T	0.3493	ambiguous	0.3409	ambiguous	-0.74	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
G/V	0.543	ambiguous	0.5482	ambiguous	-0.29	Destabilizing	1.0	D	0.755	deleterious	D	0.538428023	None	None	N
G/W	0.7237	likely_pathogenic	0.697	pathogenic	-1.122	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
G/Y	0.6709	likely_pathogenic	0.6517	pathogenic	-0.747	Destabilizing	1.0	D	0.738	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.