TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35469	106630;106631;106632	chr2:178530086;178530085;178530084	chr2:179394813;179394812;179394811
N2AB	33828	101707;101708;101709	chr2:178530086;178530085;178530084	chr2:179394813;179394812;179394811
N2A	32901	98926;98927;98928	chr2:178530086;178530085;178530084	chr2:179394813;179394812;179394811
N2B	26404	79435;79436;79437	chr2:178530086;178530085;178530084	chr2:179394813;179394812;179394811
Novex-1	26529	79810;79811;79812	chr2:178530086;178530085;178530084	chr2:179394813;179394812;179394811
Novex-2	26596	80011;80012;80013	chr2:178530086;178530085;178530084	chr2:179394813;179394812;179394811
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-166
• Domain position: 50
• Structural Position: 125
• Q(SASA): 0.3389
• 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
S/P	None	None	0.82	N	0.451	0.43	0.36256342048	gnomAD-4.0.0	3.20718E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.73506E-06	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
S/A	0.0828	likely_benign	0.0816	benign	-0.464	Destabilizing	0.019	N	0.204	neutral	N	0.486863108	None	None	N
S/C	0.1808	likely_benign	0.1711	benign	-0.298	Destabilizing	0.001	N	0.141	neutral	N	0.508409075	None	None	N
S/D	0.3642	ambiguous	0.376	ambiguous	0.227	Stabilizing	0.633	D	0.251	neutral	None	None	None	None	N
S/E	0.4205	ambiguous	0.4251	ambiguous	0.232	Stabilizing	0.633	D	0.25	neutral	None	None	None	None	N
S/F	0.1347	likely_benign	0.1322	benign	-0.567	Destabilizing	None	N	0.173	neutral	N	0.468933495	None	None	N
S/G	0.1259	likely_benign	0.1283	benign	-0.719	Destabilizing	0.103	N	0.291	neutral	None	None	None	None	N
S/H	0.2957	likely_benign	0.2982	benign	-1.107	Destabilizing	0.858	D	0.431	neutral	None	None	None	None	N
S/I	0.1334	likely_benign	0.1358	benign	0.103	Stabilizing	0.218	N	0.455	neutral	None	None	None	None	N
S/K	0.5455	ambiguous	0.5652	pathogenic	-0.491	Destabilizing	0.362	N	0.252	neutral	None	None	None	None	N
S/L	0.0829	likely_benign	0.0828	benign	0.103	Stabilizing	0.055	N	0.401	neutral	None	None	None	None	N
S/M	0.1924	likely_benign	0.1948	benign	0.11	Stabilizing	0.858	D	0.441	neutral	None	None	None	None	N
S/N	0.147	likely_benign	0.15	benign	-0.411	Destabilizing	0.633	D	0.361	neutral	None	None	None	None	N
S/P	0.6611	likely_pathogenic	0.6792	pathogenic	-0.051	Destabilizing	0.82	D	0.451	neutral	N	0.489962425	None	None	N
S/Q	0.4258	ambiguous	0.4413	ambiguous	-0.474	Destabilizing	0.858	D	0.391	neutral	None	None	None	None	N
S/R	0.4344	ambiguous	0.459	ambiguous	-0.448	Destabilizing	0.858	D	0.453	neutral	None	None	None	None	N
S/T	0.0714	likely_benign	0.0705	benign	-0.434	Destabilizing	0.08	N	0.325	neutral	N	0.460329867	None	None	N
S/V	0.1596	likely_benign	0.1591	benign	-0.051	Destabilizing	0.055	N	0.439	neutral	None	None	None	None	N
S/W	0.2266	likely_benign	0.2271	benign	-0.608	Destabilizing	0.958	D	0.477	neutral	None	None	None	None	N
S/Y	0.1494	likely_benign	0.1497	benign	-0.315	Destabilizing	0.095	N	0.439	neutral	N	0.488596691	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.