TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22999	69220;69221;69222	chr2:178577340;178577339;178577338	chr2:179442067;179442066;179442065
N2AB	21358	64297;64298;64299	chr2:178577340;178577339;178577338	chr2:179442067;179442066;179442065
N2A	20431	61516;61517;61518	chr2:178577340;178577339;178577338	chr2:179442067;179442066;179442065
N2B	13934	42025;42026;42027	chr2:178577340;178577339;178577338	chr2:179442067;179442066;179442065
Novex-1	14059	42400;42401;42402	chr2:178577340;178577339;178577338	chr2:179442067;179442066;179442065
Novex-2	14126	42601;42602;42603	chr2:178577340;178577339;178577338	chr2:179442067;179442066;179442065
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-128
• Domain position: 50
• Structural Position: 130
• Q(SASA): 0.4496
• 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
T/I	rs755306597	-0.178	0.984	D	0.485	0.31	0.535202146198	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.67E-05	0
T/I	rs755306597	-0.178	0.984	D	0.485	0.31	0.535202146198	gnomAD-4.0.0	1.57403E-05	None	None	None	None	N	None	0	6.70961E-05	None	0	0	None	0	0	1.79921E-05	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
T/A	0.1311	likely_benign	0.1185	benign	-0.374	Destabilizing	0.64	D	0.401	neutral	N	0.485940388	None	None	N
T/C	0.5917	likely_pathogenic	0.5132	ambiguous	-0.14	Destabilizing	0.999	D	0.521	neutral	None	None	None	None	N
T/D	0.4075	ambiguous	0.3693	ambiguous	0.205	Stabilizing	0.976	D	0.399	neutral	None	None	None	None	N
T/E	0.4029	ambiguous	0.3602	ambiguous	0.109	Stabilizing	0.851	D	0.388	neutral	None	None	None	None	N
T/F	0.3609	ambiguous	0.3136	benign	-1.061	Destabilizing	0.996	D	0.585	neutral	None	None	None	None	N
T/G	0.1956	likely_benign	0.1844	benign	-0.435	Destabilizing	0.034	N	0.27	neutral	None	None	None	None	N
T/H	0.3501	ambiguous	0.2807	benign	-0.857	Destabilizing	0.999	D	0.59	neutral	None	None	None	None	N
T/I	0.3314	likely_benign	0.276	benign	-0.335	Destabilizing	0.984	D	0.485	neutral	D	0.532867543	None	None	N
T/K	0.2397	likely_benign	0.2014	benign	-0.168	Destabilizing	0.076	N	0.239	neutral	None	None	None	None	N
T/L	0.1328	likely_benign	0.1162	benign	-0.335	Destabilizing	0.919	D	0.399	neutral	None	None	None	None	N
T/M	0.1326	likely_benign	0.1192	benign	0.003	Stabilizing	0.999	D	0.49	neutral	None	None	None	None	N
T/N	0.1251	likely_benign	0.1147	benign	0.063	Stabilizing	0.968	D	0.387	neutral	N	0.498984256	None	None	N
T/P	0.4523	ambiguous	0.4394	ambiguous	-0.324	Destabilizing	0.984	D	0.49	neutral	N	0.496052038	None	None	N
T/Q	0.3154	likely_benign	0.2694	benign	-0.194	Destabilizing	0.976	D	0.482	neutral	None	None	None	None	N
T/R	0.2688	likely_benign	0.2309	benign	0.017	Stabilizing	0.952	D	0.438	neutral	None	None	None	None	N
T/S	0.0947	likely_benign	0.0864	benign	-0.123	Destabilizing	0.896	D	0.379	neutral	N	0.499349615	None	None	N
T/V	0.2667	likely_benign	0.2202	benign	-0.324	Destabilizing	0.959	D	0.37	neutral	None	None	None	None	N
T/W	0.778	likely_pathogenic	0.7366	pathogenic	-1.083	Destabilizing	0.999	D	0.622	neutral	None	None	None	None	N
T/Y	0.3987	ambiguous	0.3467	ambiguous	-0.781	Destabilizing	0.996	D	0.59	neutral	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.