Table 2.
Class 3 sequence variants not reported in the HGMDp database or other sources at the time of identification, and secondary classification after family studies
| Gene | Family |
Mutation |
N tested total |
N affected tested
†
|
N healthy tested
†
|
Primary classifi-cation $ | Secondary classifi-cation £ | |||
|---|---|---|---|---|---|---|---|---|---|---|
| cDNA | Protein | Pos | Neg | Pos | Neg | |||||
|
MFN2 |
1* |
c.250 A > G |
p.Lys84Glu |
2 |
0 |
0 |
0 |
2‡ |
3 |
3 |
| 2 |
c.1709 A > G |
p.Asn570Ser |
4 |
1 |
0 |
2 |
1 |
3 |
2¶ |
|
| 3* |
c.2146_2148 dup |
p.Ala716dup |
3 |
1 |
0 |
0 |
2‡ |
3 |
4 |
|
| 4* |
c.692C > T |
p.Ser231Phe |
2 |
0 |
0 |
0 |
2‡ |
3 |
4 |
|
|
MPZ |
1* |
c.410 G > A |
p.Gly137Asp |
3 |
3 |
0 |
0 |
0 |
3 |
3 |
| 2 |
c.103 G > A |
p.Asp35Asn |
3 |
2€ |
0 |
0 |
1 |
3 |
4 |
|
| 3* |
c.368 G > T |
p.Gly123Val |
5 |
2 |
0 |
0 |
3 |
3 |
3 |
|
| NEFL | 1* | c.1027_1029del | p.Asp343del | 1 | 1 | 0 | 0 | 0 | 3 | 3 |
†In addition to index.
$Primary classification of genetic variants in the index patient in accordance with the recommendations from the IARC Unclassified Genetic Variants Working Group; 4 = likely disease causing, 3 = uncertain, 2 = likely not disease causing [18].
£Secondary classification of genetic variants after extended family investigations.
*Sequence variants reported in a previous work [9].
‡Parents negative, de novo mutation in the first following generation. MFN2 family 1; ongoing investigation, MFN2 family 3 and 4; mutation not found in 200 control chromosomes. Paternity was genetically verified.
¶This variant was later reported with a possible association to dHMN in a single Norwegian patient [24].
€One affected carrier remotely related to an index patient identified in 2012; not included in the total material.