TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31246	93961;93962;93963	chr2:178547890;178547889;178547888	chr2:179412617;179412616;179412615
N2AB	29605	89038;89039;89040	chr2:178547890;178547889;178547888	chr2:179412617;179412616;179412615
N2A	28678	86257;86258;86259	chr2:178547890;178547889;178547888	chr2:179412617;179412616;179412615
N2B	22181	66766;66767;66768	chr2:178547890;178547889;178547888	chr2:179412617;179412616;179412615
Novex-1	22306	67141;67142;67143	chr2:178547890;178547889;178547888	chr2:179412617;179412616;179412615
Novex-2	22373	67342;67343;67344	chr2:178547890;178547889;178547888	chr2:179412617;179412616;179412615
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-151
• Domain position: 29
• Structural Position: 45
• Q(SASA): 0.6041
• Predicted PPI site: I

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	rs775611779	-0.052	0.002	N	0.379	0.101	None	gnomAD-2.1.1	1.07E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	2.34E-05	0
K/R	rs775611779	-0.052	0.002	N	0.379	0.101	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	2.94E-05	0	4.78927E-04
K/R	rs775611779	-0.052	0.002	N	0.379	0.101	None	gnomAD-4.0.0	1.30135E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.69516E-05	0	1.60118E-05

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	0.2312	likely_benign	0.2464	benign	-0.044	Destabilizing	0.25	N	0.559	neutral	None	None	None	None	I
K/C	0.6001	likely_pathogenic	0.6341	pathogenic	-0.179	Destabilizing	0.982	D	0.709	prob.delet.	None	None	None	None	I
K/D	0.5487	ambiguous	0.5985	pathogenic	0.031	Stabilizing	0.7	D	0.615	neutral	None	None	None	None	I
K/E	0.1711	likely_benign	0.1768	benign	0.063	Stabilizing	0.201	N	0.545	neutral	N	0.486553676	None	None	I
K/F	0.6938	likely_pathogenic	0.7573	pathogenic	-0.052	Destabilizing	0.947	D	0.705	prob.neutral	None	None	None	None	I
K/G	0.3983	ambiguous	0.4507	ambiguous	-0.301	Destabilizing	0.399	N	0.577	neutral	None	None	None	None	I
K/H	0.2596	likely_benign	0.2776	benign	-0.604	Destabilizing	0.947	D	0.649	neutral	None	None	None	None	I
K/I	0.2757	likely_benign	0.2919	benign	0.57	Stabilizing	0.781	D	0.716	prob.delet.	N	0.488316584	None	None	I
K/L	0.2923	likely_benign	0.3291	benign	0.57	Stabilizing	0.399	N	0.577	neutral	None	None	None	None	I
K/M	0.2049	likely_benign	0.2194	benign	0.311	Stabilizing	0.947	D	0.644	neutral	None	None	None	None	I
K/N	0.383	ambiguous	0.4068	ambiguous	0.125	Stabilizing	0.638	D	0.577	neutral	D	0.524362703	None	None	I
K/P	0.8463	likely_pathogenic	0.9088	pathogenic	0.395	Stabilizing	0.826	D	0.665	neutral	None	None	None	None	I
K/Q	0.1286	likely_benign	0.1325	benign	-0.022	Destabilizing	0.015	N	0.315	neutral	N	0.51470307	None	None	I
K/R	0.0756	likely_benign	0.0774	benign	-0.19	Destabilizing	0.002	N	0.379	neutral	N	0.496984101	None	None	I
K/S	0.316	likely_benign	0.3407	ambiguous	-0.372	Destabilizing	0.25	N	0.543	neutral	None	None	None	None	I
K/T	0.1263	likely_benign	0.1316	benign	-0.177	Destabilizing	0.638	D	0.608	neutral	N	0.425179931	None	None	I
K/V	0.2159	likely_benign	0.227	benign	0.395	Stabilizing	0.7	D	0.647	neutral	None	None	None	None	I
K/W	0.7184	likely_pathogenic	0.771	pathogenic	-0.035	Destabilizing	0.982	D	0.693	prob.neutral	None	None	None	None	I
K/Y	0.6007	likely_pathogenic	0.6396	pathogenic	0.287	Stabilizing	0.826	D	0.715	prob.delet.	None	None	None	None	I

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.