Submissions for variant NM_001845.6(COL4A1):c.2245G>A (p.Gly749Ser)

dbSNP: rs113994109

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV003226898	SCV003924007	pathogenic	not provided	2023-05-04	criteria provided, single submitter	clinical testing	Reported in 3 members of a family with porencephaly (Gould et al., 2005; Gasparini et al, 2016); also identified in an unrelated infant with intracerebral hemorrhages, brain atrophy and ventriculomegaly and in his father with minor white matter abnormalities (Vermeulen et al., 2011); Affects a glycine residue in a Gly-X-Y motif in the triple helical region of the COL4A1 gene, where the majority of pathogenic missense variants occur, and is predicted to disrupt normal protein folding and function (Weng et al., 2012; Yoneda et al., 2013); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 20166936, 17696175, 15905400, 15136694, 22914737, 33013618, 27794444, 30284656, 20818663, 26686511, 30413629, 21500141, 22522439, 23225343)
OMIM	RCV002247362	SCV000039243	pathogenic	Brain small vessel disease 1 with or without ocular anomalies	2005-05-20	no assertion criteria provided	literature only
GeneReviews	RCV002247362	SCV000055812	not provided	Brain small vessel disease 1 with or without ocular anomalies		no assertion provided	literature only
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City	RCV002247362	SCV001469220	pathogenic	Brain small vessel disease 1 with or without ocular anomalies	2020-05-06	no assertion criteria provided	clinical testing