TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18034	54325;54326;54327	chr2:178605077;178605076;178605075	chr2:179469804;179469803;179469802
N2AB	16393	49402;49403;49404	chr2:178605077;178605076;178605075	chr2:179469804;179469803;179469802
N2A	15466	46621;46622;46623	chr2:178605077;178605076;178605075	chr2:179469804;179469803;179469802
N2B	8969	27130;27131;27132	chr2:178605077;178605076;178605075	chr2:179469804;179469803;179469802
Novex-1	9094	27505;27506;27507	chr2:178605077;178605076;178605075	chr2:179469804;179469803;179469802
Novex-2	9161	27706;27707;27708	chr2:178605077;178605076;178605075	chr2:179469804;179469803;179469802
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-114
• Domain position: 67
• Structural Position: 143
• Q(SASA): 0.8051
• 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
K/R	rs747897792	0.299	0.642	N	0.277	0.12	0.178374595973	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	9.81E-05	None	0	0	0
K/R	rs747897792	0.299	0.642	N	0.277	0.12	0.178374595973	gnomAD-4.0.0	6.3743E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	5.73691E-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
K/A	0.1337	likely_benign	0.1436	benign	-0.01	Destabilizing	0.001	N	0.1	neutral	None	None	None	None	N
K/C	0.4333	ambiguous	0.4699	ambiguous	-0.138	Destabilizing	0.981	D	0.3	neutral	None	None	None	None	N
K/D	0.3022	likely_benign	0.2925	benign	0.048	Stabilizing	0.704	D	0.307	neutral	None	None	None	None	N
K/E	0.1176	likely_benign	0.1069	benign	0.08	Stabilizing	0.425	N	0.225	neutral	N	0.393986579	None	None	N
K/F	0.4907	ambiguous	0.5042	ambiguous	-0.042	Destabilizing	0.893	D	0.364	neutral	None	None	None	None	N
K/G	0.2436	likely_benign	0.2468	benign	-0.265	Destabilizing	0.003	N	0.104	neutral	None	None	None	None	N
K/H	0.1855	likely_benign	0.1894	benign	-0.572	Destabilizing	0.981	D	0.292	neutral	None	None	None	None	N
K/I	0.196	likely_benign	0.2063	benign	0.594	Stabilizing	0.27	N	0.311	neutral	N	0.510371033	None	None	N
K/L	0.2019	likely_benign	0.2047	benign	0.594	Stabilizing	0.329	N	0.259	neutral	None	None	None	None	N
K/M	0.1401	likely_benign	0.1393	benign	0.349	Stabilizing	0.944	D	0.295	neutral	None	None	None	None	N
K/N	0.1974	likely_benign	0.1896	benign	0.165	Stabilizing	0.642	D	0.209	neutral	N	0.403256636	None	None	N
K/P	0.7427	likely_pathogenic	0.6892	pathogenic	0.423	Stabilizing	0.828	D	0.368	neutral	None	None	None	None	N
K/Q	0.1025	likely_benign	0.0975	benign	0.02	Stabilizing	0.784	D	0.281	neutral	N	0.4534776	None	None	N
K/R	0.0828	likely_benign	0.0779	benign	-0.146	Destabilizing	0.642	D	0.277	neutral	N	0.428888587	None	None	N
K/S	0.1834	likely_benign	0.1903	benign	-0.329	Destabilizing	0.004	N	0.076	neutral	None	None	None	None	N
K/T	0.0913	likely_benign	0.094	benign	-0.135	Destabilizing	0.27	N	0.277	neutral	N	0.491091839	None	None	N
K/V	0.1429	likely_benign	0.1531	benign	0.423	Stabilizing	0.001	N	0.088	neutral	None	None	None	None	N
K/W	0.6274	likely_pathogenic	0.6209	pathogenic	-0.034	Destabilizing	0.995	D	0.291	neutral	None	None	None	None	N
K/Y	0.3983	ambiguous	0.3932	ambiguous	0.294	Stabilizing	0.944	D	0.355	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.