Table 7 Information about the COL4A4 variant

Type of Variant

Nonsense

RefSeq

NM_000092.5

HGVS Coding

c.5007del

HGVS Protein

p.Leu1670Ter

Cytogenetic Location

2q36.3

ExAC Frequency

0

gnomAD Control Frequency

0

PhyloP100way Score

8.032

ClinVar Invitae Accession Number

SCV001580980.2

ClinVar GeneDx Accession Number

SCV001993731.1

Natera ACMG Criteria Scores

PVS1_strong, PM2_supporting, PP1_supporting

Invitae Sherloc System Criteria and Point Values

•LOF variant and LOF is a known mechanism of disease in COL4A4 with absence in the ExAC population (+ 2.5 points for Sherloc scoring system and similar to Natera’s PVS1 and PM2)

•Discovery of another patient in their laboratory that had a pathogenic variant upstream this case’s variant (+ 2.5 points for Sherloc scoring system and did not directly correlate with evidence from the ACMG criteria)

GeneDx ACMG Criteria Score

PVS1 (strength decreased to strong)